Prospective randomized studies of maintenance therapy for patients with squamous non-small-cell lung cancer are lacking. In the present study, patients without disease progression after induction treatment were randomized 2:1 to maintenance nanoparticle albumin-bound paclitaxel plus best supportive care or best supportive care alone. The primary endpoint (progression-free survival) was not met. Given the current treatment paradigm, these findings can be expected to minimally affect treatment practice. Background: We evaluated maintenance nanoparticle albumin-bound (nab) paclitaxel in the treatment of advanced squamous non-small-cell lung cancer. Patients and Methods: Patients with treatment-naive squamous non-smallcell lung cancer received four 21-day cycles of nab-paclitaxel 100 mg/m(2) on days 1, 8, 15 plus carboplatin area under the curve 6 on day 1 as induction therapy. Patients without disease progression after induction were randomized 2:1 to maintenance nab-paclitaxel 100 mg/m(2) (days 1 and 8 every 21 days) plus best supportive care (BSC) or BSC alone. The primary endpoint was progression-free survival (PFS). Secondary endpoints included safety and overall survival (OS). Results: Overall, 420 patients had received induction therapy; 202 (nab-paclitaxel plus BSC, 136; BSC, 66) had received maintenance therapy. Enrollment was discontinued after a preplanned interim futility analysis (patients could remain in the study at the investigator's discretion). The median PFS was 3.12 months for nab-paclitaxel plus BSC 2.60 months for BSC; the difference was not statistically significant (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.61-1.19; P = .36). The median OS (median follow-up, 24.2 months) was 17.18 months for nab-paclitaxel plus BSC and 12.16 months for BSC (HR, 0.70; 95% CI, 0.48-1.02; nominal P = .07). An updated analysis (median followup, 28.4 months) revealed a median OS of 17.61 months for nab-paclitaxel plus BSC and 12.16 months for BSC (HR, 0.68; 95% CI, 0.47-0.98; nominal P= .037). The most frequent grade 3 and 4 treatment-emergent adverse events for the entire study were neutropenia (53.1% [nab-paclitaxel plus BSC] vs. 50.0% [BSC]) and anemia (33.1% [nabpaclitaxel plus BSC] vs. 32.3% [BSC]). Only peripheral neuropathy had occurred in > 5% of patients during maintenance therapy (13.1%; nab-paclitaxel plus BSC). Conclusions: The results of the ABOUND.sqm did not meet the primary endpoint of PFS. An updated OS analysis revealed a trend favoring nab-paclitaxel plus BSC. (C) 2020 Published by Elsevier Inc.

PURPOSE Limited data exist on the optimal duration of immunotherapy, including for non–small-cell lung cancer (NSCLC). We present an exploratory analysis of CheckMate 153, a largely community-based phase IIIb/IV study, to evaluate the impact of 1-year fixed-duration versus continuous therapy on the efficacy and safety of nivolumab. METHODS Patients with previously treated advanced NSCLC received nivolumab monotherapy (3 mg/kg every 2 weeks). Those still receiving treatment at 1 year, including patients perceived to be deriving benefit despite radiographic progression, were randomly assigned to continue nivolumab until disease progression or unacceptable toxicity or to stop nivolumab with the option of on-study retreatment after disease progression (1-year fixed duration). RESULTS Of 1,428 patients treated, 252 were randomly assigned to continuous (n = 127) or 1-year fixed-duration (n = 125) treatment (intent-to-treat [ITT] population). Of these, 89 and 85 patients in the continuous and 1-year fixed-duration arms, respectively, had not progressed (progression-free survival [PFS] population). With minimum post–random assignment follow-up of 13.5 months, median PFS was longer with continuous versus 1-year fixed-duration treatment (PFS population: 24.7 months v 9.4 months; hazard ratio [HR], 0.56 [95% CI, 0.37 to 0.84]). Median overall survival from random assignment was longer with continuous versus 1-year fixed-duration treatment in the PFS (not reached v 32.5 months; HR, 0.61 [95% CI, 0.37 to 0.99]) and ITT (not reached v 28.8 months; HR, 0.62 [95% CI, 0.42 to 0.92]) populations. Few new-onset treatment-related adverse events occurred. No new safety signals were identified. CONCLUSION To our knowledge, these findings from an exploratory analysis represent the first randomized data on continuous versus fixed-duration immunotherapy in previously treated advanced NSCLC and suggest that continuing nivolumab beyond 1 year improves outcomes.

BACKGROUND:Many patients with metastatic non-small-cell lung cancer (mNSCLC) experience disease progression after first- and second-line treatment; more treatment options are required for these patients. ARCTIC, a phase III, randomized, open-label study, assessed durvalumab ± tremelimumab versus standard of care (SoC) as ≥ third-line treatment of mNSCLC. PATIENTS AND METHODS:ARCTIC comprised two independent sub-studies. Study A: 126 patients with ≥25% of tumor cells (TCs) expressing programmed cell death ligand-1 (PD-L1) were randomized (1 : 1) to durvalumab [up to 12 months 10 mg/kg every 2 weeks (q2w)] or SoC. Study B: 469 patients with PD-L1 TC <25% were randomized (3 : 2 : 2 : 1) to durvalumab + tremelimumab (12 weeks durvalumab 20 mg/kg + tremelimumab 1 mg/kg q4w then 34 weeks durvalumab 10 mg/kg q2w), SoC, durvalumab (up to 12 months 10 mg/kg q2w), or tremelimumab (24 weeks 10 mg/kg q4w then 24 weeks q12w). Primary end points: overall survival (OS) and progression-free survival (PFS) for durvalumab versus SoC (study A; descriptive only) and durvalumab + tremelimumab versus SoC (study B). RESULTS:Study A: median OS 11.7 (durvalumab) versus 6.8 (SoC) months {hazard ratio (HR) 0.63 [95% confidence interval (CI), 0.42-0.93]}; median PFS 3.8 (durvalumab) versus 2.2 (SoC) months [HR 0.71 (95% CI, 0.49-1.04)]. Study B: median OS 11.5 (durvalumab + tremelimumab) versus 8.7 (SoC) months [HR 0.80 (95% CI, 0.61-1.05); P = 0.109]. Median PFS of 3.5 months for both groups [HR 0.77 (95% CI, 0.59-1.01); P = 0.056]. Treatment-related grade 3/4 adverse events: 9.7% (durvalumab) and 44.4% (SoC; study A) and 22.0% (durvalumab + tremelimumab) and 36.4% (SoC; study B). CONCLUSIONS:In heavily pretreated patients with mNSCLC, durvalumab demonstrated clinically meaningful improvements in OS and PFS versus SoC (patients with PD-L1 TC ≥25%); numerical improvements in OS and PFS for durvalumab + tremelimumab versus SoC were observed (patients with PD-L1 TC <25%). Safety profiles were consistent with previous studies. TRIAL REGISTRATION:Clinicaltrials.gov identifier: NCT02352948.

BACKGROUND:This randomized, double-blinded, phase II trial evaluated the efficacy of carboplatin and pemetrexed plus either apatorsen, an antisense oligonucleotide targeting heat shock protein (Hsp) 27 mRNA, or placebo in patients with previously untreated metastatic nonsquamous non-small cell lung cancer (NSCLC).METHODS:Patients were randomized 1:1 to Arm A (carboplatin/pemetrexed plus apatorsen) or Arm B (carboplatin/pemetrexed plus placebo). Treatment was administered in 21-day cycles, with restaging every two cycles, until progression or intolerable toxicity. Serum Hsp27 levels were analyzed at baseline and during treatment. The primary endpoint was progression-free survival (PFS); secondary endpoints included overall survival (OS), objective response rate, and toxicity.RESULTS:The trial enrolled 155 patients (median age 66 years; 44% Eastern Cooperative Oncology Group performance status 0). Toxicities were similar in the 2 treatment arms; cytopenias, nausea, vomiting, and fatigue were the most frequent treatment-related adverse events. Median PFS and OS were 6.0 and 10.8 months, respectively, for Arm A, and 4.9 and 11.8 months for Arm B (differences not statistically significant). Overall response rates were 27% for Arm A and 32% for Arm B. Sixteen patients (12%) had high serum levels of Hsp27 at baseline. In this small group, patients who received apatorsen had median PFS of 10.8 months, and those who received placebo had median PFS 4.8 months.CONCLUSION:The addition of apatorsen to carboplatin and pemetrexed was well tolerated but did not improve outcomes in patients with metastatic nonsquamous NSCLC cancer in the first-line setting.IMPLICATIONS FOR PRACTICE:This randomized, double-blinded, phase II trial evaluated the efficacy of carboplatin and pemetrexed plus either apatorsen, an antisense oligonucleotide targeting heat shock protein 27 mRNA, or placebo in patients with previously untreated metastatic nonsquamous non-small cell lung cancer (NSCLC). The addition of apatorsen to carboplatin and pemetrexed was well tolerated but did not improve outcomes in patients with metastatic nonsquamous NSCLC cancer in the first-line setting.

Background: Atezolizumab (atezo) (anti-PD-L1) monotherapy improves overall survival (OS) vs docetaxel in 2L+ NSCLC regardless of PD-L1 status; phase 3, 1L studies have shown clinical benefit of atezo plus chemotherapy and atezo in combination with bevacizumab and chemotherapy. IMpower130 (NCT02367781) evaluated atezo + CnP vs CnP in patients (pts) with measurable (RECIST v1.1) stage IV non-squamous NSCLC. Methods: Pts (randomized 2:1) received atezo (1200 mg IV q3w) + CnP (carboplatin: AUC 6 q3w; nab-paclitaxel: 100 mg/m2 IV qw) (Arm A) or CnP (Arm B), for 4 or 6 21-day cycles and maintenance (Arm A: atezo until loss of clinical benefit; Arm B: best supportive care or pemetrexed q3w until disease progression [PD]). Crossover to atezo at PD was initially permitted for Arm B pts. Co-primary endpoints were investigator-assessed PFS and OS (ITT-WT population: EGFR-WT/ALK-negative). Secondary endpoints were OS and PFS (ITT population and by PD-L1 expression), response rate and safety. ITT population could be formally tested for OS/PFS if ITT-WT OS was positive. Results: 723 ITT (679 ITT-WT) pts were enrolled. Statistically significant, clinically meaningful improvements in OS and statistically significant and clinically meaningful improvements in PFS (ITT and ITT-WT) were observed in Arm A vs Arm B (table). PFS and OS benefit was observed in all PD-L1 subgroups, and consistently across all subgroups, except in pts with liver metastases and EGFR/ALK genomic alterations. In treated pts, 73.2% (Arm A) vs 60.3% (Arm B) had grade 3-4 treatment-related adverse events. Conclusions: Overall, IMpower130 showed statistically significant, clinically meaningful improvements in OS and statistically significant improvements in PFS with atezo + CnP, vs CnP, in 1L, stage IV non-squamous NSCLC, in this predominantly ITT-WT population. No new safety signals were identified. Table.IMpower130 Efficacy AnalysesArm A Atezo + CnPArm B CnPITT-WTn = 451n = 228Median OS (95% CI)18.6 mo (16.0-21.2)13.9 mo (12.0-18.7)HR (95% CI; P value)0.79 (0.64-0.98; 0.033)12-mo OS (95% CI)63.1% (58.59-67.66)55.5% (48.89-62.17)Median PFS (95% CI)7.0 mo (6.2-7.3)5.5 mo (4.4-5.9)HR (95% CI; P value)0.64 (0.54-0.77; < 0.0001)12-mo PFS (95% CI)29.1% (24.83-33.44)14.1% (9.37-18.76)n = 447n = 226Confirmed ORR (investigator assessed) (95% CI)49.2% (44.49-53.96)31.9% (25.84-38.36)n = 220n = 72Median DOR (95% CI)8.4 mo (6.9-11.8)6.1 mo (5.5-7.9)PD-L1 highan = 88n = 42Median OS (95% CI)17.4 mo (14.78-NA)16.9 mo (10.94-NA)HR (95% CI)0.84 (0.51-1.39)Median PFS (95% CI)6.4 mo (5.49-9.76)4.6 mo (3.22-7)HR (95% CI)0.51 (0.34-0.77)PD-L1 lowan = 128n = 65Median OS (95% CI)23.7 mo (18.63-NA)15.9 mo (12.32-25.63)HR (95% CI)0.70 (0.45-1.08)Median PFS (95% CI)8.3 mo (7.16-10.35)6.0 mo (5.29-6.93)HR (95% CI)0.61 (0.43-0.85)PD-L1 negativean = 235n = 121Median OS (95% CI)15.2 mo (12.88-19.15)12.0 mo (8.97-17.71)HR (95% CI)0.81 (0.61-1.08)Median PFS (95% CI)6.2 mo (5.52-7.16)4.7 mo (4.11-5.72)HR (95% CI)0.72 (0.56-0.91)ITTn = 483n = 240Median OS (95% CI)18.1 mo (15.3-20.8)13.9 mo (12.0-18.2)HR (95% CI; P value)0.80 (0.65-0.99; 0.039)Median PFS (95% CI)7.0 mo (6.3-7.3)5.6 mo (4.5-5.9)HR (95% CI; P value)0.65 (0.54-0.77; < 0.0001)a PD-L1 high (TC3 or IC3): Patients with PD-L1 expression in ≥ 50% of tumor cells or ≥ 10% of tumor-infiltrating immune cells; PD-L1 low (TC1/2 or IC1/2): Patients with PD-L1 expression in ≥ 1% and < 50% of tumor cells or ≥ 1% and <10% of tumor-infiltrating immune cells; and PD-L1 negative (TC0 and IC0): Patients with PD-L1 expression in <1% of tumor cells and < 1% of tumor-infiltrating immune cells. Data cut-off: 15 March 2018. Minimum follow up: 13 months. NCT02367781.DOR, duration of response; HR, hazard ratio; IC, immune cells; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; TC, tumor cells. Citation Format: Howard L. West, Michael McCleod, Maen Hussein, Alessandro Morabito, Achim Rittmeyer, Henry J. Conter, Hans-Georg Kopp, Davey Daniel, Steven McCune, Tarek Mekhail, Alona Zer, Niels Reinmuth, Ahad Sadiq, Venice Archer, Tania Ochi Lohmann, Helen Jessop, Lijia Wang, Marcin Kowanetz, Alan Sandler, Federico Cappuzzo. IMpower130: Progression-free survival (PFS) and safety analysis from a randomized phase 3 study of carboplatin + nab-paclitaxel (CnP) with or without atezolizumab as first-line (1L) therapy in advanced non-squamous NSCLC [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr CT200.

nab-Paclitaxel maintenance therapy after nab-paclitaxel/carboplatin induction in patients with advanced squamous NSCLC was evaluated in the phase III, randomized, controlled, open-label, multicenter ABOUND.sqm trial. At the 12-month follow-up, there was no statistically significant difference in progression-free survival (PFS) between patients randomized to maintenance nab-paclitaxel + best supportive care (BSC) vs BSC alone. However, a trend of an overall survival (OS) advantage was observed with nab-paclitaxel + BSC vs BSC alone. Here we report the 18-month follow-up of OS. Patients (aged ≥18 years) with histologically or cytologically confirmed stage IIIB/IV squamous NSCLC and no prior chemotherapy were eligible. Patients received four 21-day cycles of nab-paclitaxel 100 mg/m2 (days 1, 8, and 15) plus carboplatin AUC 6 (day 1) as induction. Patients with radiologically assessed complete or partial response or stable disease without clinical progression after 4 cycles were randomized 2:1 to maintenance nab-paclitaxel 100 mg/m2 (days 1 and 8 of each 21-day cycle) plus BSC or BSC alone until disease progression. The primary efficacy analysis was performed on the ITT population. PFS from randomization into the maintenance part of the study was the primary endpoint. Secondary endpoints included safety, OS (from randomization), and response. 420 patients received induction therapy; 202 were randomized to maintenance nab-paclitaxel + BSC (n = 136) or BSC alone (n = 66). The median PFS in patients in the nab-paclitaxel + BSC arm vs those in the BSC-alone arm was 3.1 vs 2.6 months (HR, 0.85; P = 0.349), respectively; the median OS was 17.8 vs 12.2 months (HR, 0.71; P = 0.058), respectively. The overall response rate was 69.1% vs 57.6% (RRR, 1.20; P = 0.087). Following the maintenance part, 73.5% (nab-paclitaxel + BSC) and 68.2% (BSC alone) of patients received subsequent anti-cancer treatment. Over the entire study, the most frequent grade 3/4 TEAEs were neutropenia (53.1% vs 50.0%) and anemia (33.1% vs 32.3%); only peripheral neuropathy occurred in ≥ 5% of patients during maintenance (13.1% in the nab-paclitaxel + BSC arm). Although PFS and OS differences were not statistically significant in the ITT population, the 18-month follow-up of OS demonstrated the feasibility of nab-paclitaxel maintenance therapy for patients with anced squamous NSCLC. ClinicalTrials.gov identifier: NCT02027428

Background Atezolizumab (a monoclonal antibody against PD-L1), which restores anticancer immunity, improved overall survival in patients with previously treated non-small-cell lung cancer and also showed clinical benefit when combined with chemotherapy as first-line treatment of non-small-cell lung cancer. IMpower130 aimed to assess the efficacy and safety of atezolizumab plus chemotherapy versus chemotherapy alone as first-line therapy for non-squamous non-small-cell lung cancer. Methods IMpower130 was a multicentre, randomised, open-label, phase 3 study done in 131 centres across eight countries (the USA, Canada, Belgium, France, Germany, Italy, Spain, and Israel). Eligible patients were aged 18 years or older, and had histologically or cytologically confirmed stage IV non-squamous non-small-cell lung cancer, an Eastern Cooperative Oncology Group performance status of 0 or 1, and received no previous chemotherapy for stage IV disease. Patients were randomly assigned (2:1; permuted block [block size of six] with an interactive voice or web response system) to receive atezolizumab (1200 mg intravenously every 3 weeks) plus chemotherapy (carboplatin [area under the curve 6 mg/mL per min every 3 weeks] plus nab-paclitaxel [100 mg/m(2) intravenously every week]) or chemotherapy alone for four or six 21-day cycles followed by maintenance therapy. Stratification factors were sex, baseline liver metastases, and PD-L1 tumour expression. Co-primary endpoints were investigator-assessed progression-free survival and overall survival in the intention-to-treat wild-type (ie, EGFR(wt) and ALK(wt)) population. The safety population included patients who received at least one dose of the study drug. This study is registered with ClinicalTrials.gov, number NCT02367781. Findings Between April 16, 2015, and Feb 13, 2017, 724 patients were randomly assigned and 723 were included in the intention-to-treat population (one patient died before randomisation, but was assigned to a treatment group; this patient was excluded from the intention-to-treat population) of the atezolizumab plus chemotherapy group (483 patients in the intention-to-treat population and 451 patients in the intention-to-treat wild-type population) or the chemotherapy group (240 patients in the intention-to-treat population and 228 patients in the intention-to-treat wild-type population). Median follow-up in the intention-to-treat wild-type population was similar between groups (18.5 months [IQR 15.2-23.6] in the atezolizumab plus chemotherapy group and 19.2 months [15.4-23.0] in the chemotherapy group). In the intention-to-treat wild-type population, there were significant improvements in median overall survival (18.6 months [95% CI 16.0-21.2] in the atezolizumab plus chemotherapy group and 13.9 months [12.0-18.7] in the chemotherapy group; stratified hazard ratio [HR] 0.79 [95% CI 0.64-0.98]; p=0.033) and median progression-free survival (7.0 months [95% CI 6.2-7.3] in the atezolizumab plus chemotherapy group and 5.5 months [4.4-5.9] in the chemotherapy group; stratified HR 0.64 [95% CI 0.54-0.77]; p<0.0001]). The most common grade 3 or worse treatment-related adverse events were neutropenia (152 [32%] of 473 in the atezolizumab plus chemotherapy group vs 65 [28%] of 232 in the chemotherapy group), anaemia (138 [29%] vs 47 [20%]), and decreased neutrophil count (57 [12%] vs 19 [8%]). Treatment-related serious adverse events were reported in 112 (24%) of 473 patients in the atezolizumab plus chemotherapy group and 30 (13%) of 232 patients in the chemotherapy group. Treatment-related (any treatment) deaths occurred in eight (2%) of 473 patients in the atezolizumab plus chemotherapy group and one (<1%) of 232 patients in the chemotherapy group. Interpretation IMpower130 showed a significant and clinically meaningful improvement in overall survival and a significant improvement in progression-free survival with atezolizumab plus chemotherapy versus chemotherapy as first-line treatment of patients with stage IV non-squamous non-small-cell lung cancer and no ALK or EGFR mutations. No new safety signals were identified. This study supports the benefit of atezolizumab, in combination with platinum-based chemotherapy, as first-line treatment of metastatic non-small-cell lung cancer. Copyright (C) 2019 Elsevier Ltd. All rights reserved.

INTRODUCTION:CheckMate 153 (NCT02066636) is a phase 3B/4 study assessing nivolumab in previously treated patients with advanced NSCLC. Eligibility criteria allowed enrollment of patients with poor prognostic features of advanced age or diminished Eastern Cooperative Oncology Group performance status (ECOG PS), which are typically underrepresented in or excluded from randomized controlled trials. METHODS:Patients with stage IIIB or IV NSCLC and an ECOG PS of 0 to 2 with disease progression after at least one systemic therapy received nivolumab (3 mg/kg every 2 weeks) until progression, unacceptable toxicity, or consent withdrawal. The primary end point was the incidence of grade 3 to 5 select treatment-related adverse events (TRAEs). RESULTS:Among 1426 treated patients, 556 (39%) were aged 70 years or older and 128 (9%) had an ECOG PS of 2. The median treatment duration was 3.2 months. Across subgroups and the overall population, the incidences of select grade 3 to 5 TRAEs (6%-9%) and grade 3 or 4 TRAEs (12%-14%) were similar. One grade 5 TRAE was documented. The median overall survival time was comparable in the overall population (9.1 months) and patients aged 70 years or older (10.3 months) but shorter in patients with an ECOG PS of 2 (4.0 months). Patient-reported outcomes generally improved. CONCLUSIONS:Data from this large predominantly community-based study, which included patients aged 70 years or older and with an ECOG PS of 2, are consistent with registrational studies. As expected, the median overall survival for patients with an ECOG PS of 2 was lower than for the overall population but comparable with historical data.

Background: Atezo (anti-PD-L1) monotherapy improves overall survival (OS) vs docetaxel in 2L+ NSCLC, regardless of PD-L1 status; phase 3, 1L studies have shown the clinical benefit of atezo plus chemotherapy. IMpower130 (NCT02367781) evaluated atezo + CnP vs CnP in patients (pts) with measurable (RECIST v1.1) stage IV non-squamous NSCLC. Methods: Pts (randomised 2:1) received atezo (1200 mg IV q3w) + CnP (carboplatin: AUC 6 q3w; nab-paclitaxel: 100 mg/m2 IV qw) (Arm A) or CnP (Arm B), for 4 or 6 21-day cycles and maintenance (Arm A: atezo until loss of clinical benefit; Arm B: best supportive care or pemetrexed q3w until disease progression [PD]). Crossover to atezo at PD was initially permitted for Arm B pts. Co-primary endpoints: investigator-assessed PFS and OS (ITT-WT population: EGFR-WT/ALK-negative). Secondary endpoints: OS and PFS (ITT population and by PD-L1 expression), response rate and safety. ITT population could be formally tested for OS/PFS if ITT-WT OS was positive. Results: 723 ITT (679 ITT-WT) pts were enrolled. Statistically significant, clinically meaningful improvements in OS and statistically significant improvements in PFS (ITT and ITT-WT) were observed in Arm A vs Arm B (table). PFS and OS benefit was observed in all PD-L1 subgroups, and consistently across all subgroups, except in pts with liver metastases and EGFR/ALK genomic alterations. In treated pts, 73.2% (Arm A) vs 60.3% (Arm B) had grade 3–4 treatment-related adverse events. Conclusions: Overall, IMpower130 showed statistically significant, clinically meaningful improvements in OS and statistically significant improvements in PFS with atezo + CnP, vs CnP, in 1L, stage IV non-squamous NSCLC, in this predominantly ITT-WT population. No new safety signals were identified.Table: LBA53IMpower 130 efficacy analysesArm A Atezo + CnPArm B CnPITT-WTn = 451n = 228Median OS (95% CI)18.6 mo (16.0–21.2)13.9 mo (12.0–18.7)HR (95% CI; P value)0.79 (0.64–0.98; 0.033)12-mo OS (95% CI)63.1% (58.59–67.66)55.5% (48.89–62.17)Median PFS (95% CI)7.0 mo (6.2–7.3)5.5 mo (4.4–5.9)HR (95% CI; P value)0.64 (0.54–0.77; <0.0001)12-mo PFS (95% CI)29.1% (24.83–33.44)14.1% (9.37–18.76)n = 447n = 226Confirmed ORR (investigator assessed) (95% CI)49.2% (44.49–53.96)31.9% (25.84–38.36)n = 220n = 72Median DOR (95% CI)8.4 mo (6.9–11.8)6.1 mo (5.5–7.9)PD-L1 highaPD-L1 high (TC3 or IC3): Patients with PD-L1 expression in≥50% of tumour cells or≥10% of tumour-infiltrating immune cells; PD-L1 low (TC1/2 or IC1/2): Patients with PD-L1 expression in≥1% and <50% of tumour cells or≥1% and <10% of tumour-infiltrating immune cells; and PD-L1 negative (TC0 and IC0): Patients with PD-L1 expression in<1% of tumour cells and <1% of tumour-infiltrating immune cells. Data cut-off: 15 March 2018. Minimum follow up: 13 months. NCT02367781. DOR, duration of response; HR, hazard ratio; IC, immune cells; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; TC, tumour cells.n = 88n = 42Median OS (95% CI)17.4 mo (14.78–NA)16.9 mo (10.94–NA)HR (95% CI)0.84 (0.51–1.39)Median PFS (95% CI)6.4 mo (5.49–9.76)4.6 mo (3.22–7)HR (95% CI)0.51 (0.34–0.77)PD-L1 lowaPD-L1 high (TC3 or IC3): Patients with PD-L1 expression in≥50% of tumour cells or≥10% of tumour-infiltrating immune cells; PD-L1 low (TC1/2 or IC1/2): Patients with PD-L1 expression in≥1% and <50% of tumour cells or≥1% and <10% of tumour-infiltrating immune cells; and PD-L1 negative (TC0 and IC0): Patients with PD-L1 expression in<1% of tumour cells and <1% of tumour-infiltrating immune cells. Data cut-off: 15 March 2018. Minimum follow up: 13 months. NCT02367781. DOR, duration of response; HR, hazard ratio; IC, immune cells; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; TC, tumour cells.n = 128n = 65Median OS (95% CI)23.7 mo (18.63–NA)15.9 mo (12.32–25.63)HR (95% CI)0.70 (0.45–1.08)Median PFS (95% CI)8.3 mo (7.16–10.35)6.0 mo (5.29–6.93)HR (95% CI)0.61 (0.43–0.85)PD-L1 negativeaPD-L1 high (TC3 or IC3): Patients with PD-L1 expression in≥50% of tumour cells or≥10% of tumour-infiltrating immune cells; PD-L1 low (TC1/2 or IC1/2): Patients with PD-L1 expression in≥1% and <50% of tumour cells or≥1% and <10% of tumour-infiltrating immune cells; and PD-L1 negative (TC0 and IC0): Patients with PD-L1 expression in<1% of tumour cells and <1% of tumour-infiltrating immune cells. Data cut-off: 15 March 2018. Minimum follow up: 13 months. NCT02367781. DOR, duration of response; HR, hazard ratio; IC, immune cells; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; TC, tumour cells.n = 235n = 121Median OS (95% CI)15.2 mo (12.88–19.15)12.0 mo (8.97–17.71)HR (95% CI)0.81 (0.61–1.08)Median PFS (95% CI)6.2 mo (5.52–7.16)4.7 mo (4.11–5.72)HR (95% CI)0.72 (0.56–0.91)ITTn = 483n = 240Median OS (95% CI)18.1 mo (15.3–20.8)13.9 mo (12.0–18.2)HR (95% CI; P value)0.80 (0.65–0.99; 0.039)Median PFS (95% CI)7.0 mo (6.3–7.3)5.6 mo (4.5–5.9)HR (95% CI; P value)0.65 (0.54–0.77; <0.0001)a PD-L1 high (TC3 or IC3): Patients with PD-L1 expression in ≥ 50% of tumour cells or ≥ 10% of tumour-infiltrating immune cells; PD-L1 low (TC1/2 or IC1/2): Patients with PD-L1 expression in ≥ 1% and <50% of tumour cells or ≥ 1% and <10% of tumour-infiltrating immune cells; and PD-L1 negative (TC0 and IC0): Patients with PD-L1 expression in < 1% of tumour cells and <1% of tumour-infiltrating immune cells. Data cut-off: 15 March 2018. Minimum follow up: 13 months. NCT02367781. DOR, duration of response; HR, hazard ratio; IC, immune cells; ORR, objective response rate; OS, overall survival; PFS, progression-free survival; TC, tumour cells. Open table in a new tab Clinical trial identification: NCT02367781 (20 February 2015). Editorial acknowledgement: Support for third-party writing assistance for this abstract, furnished by Islay Steele, PhD, of Health Interactions, was provided by F. Hoffmann-La Roche Ltd, Basel, Switzerland. Legal entity responsible for the study: F. Hoffmann-La Roche Ltd. Funding: F. Hoffmann-La Roche Ltd. Disclosure: F. Cappuzzo: Membership of advisory board: Roche, AstraZeneca, BMS, Pfizer, MSD. A. Morabito: Membership of advisory board: Astra Zeneca, Boehringer Ingelheim, MSD, Pfizer; Speaker bureaus: Boehringer Ingelheim, BMS, Amag, Incyte, Heron. A. Rittmeyer: Grants: AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, MSD, Pfizer, Roche outside the submitted work. H-G. Kopp: Membership of advisory board: Roche, MSD, BMS. A. Zer: Membership of advisory board: AstraZeneca, Lilly, Boehringer Ingelheim. N. Reinmuth: Membership of advisory board: Roche, BMS, Astra Zeneca, MSD. V. Archer: Employee of Roche Products Limited. T. Ochi Lohmann: Employee of F. Hoffmann-La Roche. L. Wang, M. Kowanetz, W. Lin, A. Sandler: Employee of Genentech, Inc. H. West: Personal fees: AstraZeneca, Genentech/Roche, Pfizer (during the conduct of the study); Personal fees: Boehringer-Ingelheim (outside the submitted work). All other authors have declared no conflicts of interest.

Nivolumab has been administered using a 60-min infusion time. Reducing this time to 30 min would benefit both patients and infusion facilities. This analysis compared the safety of 30- and 60-min infusions of nivolumab in patients with previously treated advanced non-small cell lung cancer.

Background: Combining atezolizumab (atezo; anti–PD-L1) and chemotherapy (chemo) may further improve outcomes in NSCLC by enhancing immunomodulatory effects. IMpower131 (NCT02367794) is a randomised Ph III trial of atezo + chemo vs chemo alone in 1L Stage IV squamous NSCLC. In the primary analysis, PFS benefit was seen with atezo + carboplatin (carbo) + nab-paclitaxel (nab-pac) vs carbo + nab-pac (HR, 0.71; 95% CI: 0.60, 0.85; P = 0.0001), with a tolerable safety profile. Here we report updated results at the second interim OS analysis (Arm B vs C). Methods: 1021 pts were randomised 1:1:1 to Arm A (atezo 1200 mg q3w + carbo AUC 6 q3w + paclitaxel 200 mg/m2 q3w), Arm B (atezo + carbo + nab-pac 100 mg/m2 qw) or Arm C (carbo + nab-pac). Pts received chemo ± atezo for 4 or 6 cycles per investigator choice, followed by atezo maintenance (Arms A and B). Pts had chemo-naive, Stage IV squamous NSCLC and were stratified by sex, baseline liver metastases and PD-L1 expression. Coprimary endpoints are investigator-assessed PFS and OS in the ITT population.Table: LBA65Arm B atezo + carbo + nab-pac N = 343Arm C carbo + nab-pac N = 340Region of enrolment, % Eastern Europe Rest of Europe North America/Australia Central/South America Asia Pacific21.9 33.8 25.4 7.0 12.022.6 36.5 23.8 6.8 10.3≥ 1 subsequent anti-cancer therapy, % Immunotherapy33.8 5.557.6 42.6Median PFS, moaPFS was updated as a post-hoc analysis.6.55.6 HR (95% CI)0.74 (0.62, 0.87)Median OS, mo14.614.3 HR (95% CI); P value0.92 (0.76, 1.12); 0.41Confirmed ORR, %49.441.3Median DOR, mo7.55.2 HR (95% CI)0.57 (0.45, 0.74)CI, confidence interval; DOR, duration of response; HR, hazard ratio; ORR, objective response rate; PFS, progression-free survival.a PFS was updated as a post-hoc analysis. Open table in a new tab CI, confidence interval; DOR, duration of response; HR, hazard ratio; ORR, objective response rate; PFS, progression-free survival. Results: At data cutoff (20 April 2018), minimum follow-up was 12.8 mo. Median OS was 14.6 mo in Arm B vs 14.3 mo in Arm C (HR, 0.92; 95% CI: 0.76, 1.12; P = 0.41; Table). Median PFS was 6.5 mo in Arm B vs 5.6 mo in Arm C (HR, 0.74; 95% CI: 0.62, 0.87). Treatment-related AEs occurred in 95% (Arm B) and 91% (Arm C) of pts and were Grade 3-4 in 68% (Arm B) and 57% (Arm C) of pts. Region of enrolment was balanced between treatment arms; 6% (Arm B) and 43% (Arm C) of pts received cancer immunotherapy in second or later lines. Conclusions: At this second interim OS analysis, OS remained comparable in Arm B vs C; OS did not cross the boundary and continues to be followed. IMpower131 continued to show improved PFS in Arm B vs C. The safety of atezo + carbo + nab-pac was consistent with the profile for each agent, with no new or unexpected signals. Clinical trial identification: NCT02367794. Editorial acknowledgement: Kia Walcott, PhD, of Health Interactions, Inc. Legal entity responsible for the study: F. Hoffmann-La Roche AG. Funding: F. Hoffmann-La Roche AG. Disclosure: M.A. Socinski: Honoraria, speakers bureau, research funding: Genentech. A. Rittmeyer: Grants as advisor or speaker: AbbVie, AstraZeneca, BMS, Boehringer Ingelheim, Eli Lilly, MSD, Pfizer, Roche. F. Orlandi: Honoraria for advisory boards: Astrazeneca, Amgen-Roche, Boehringer Ingelheim, MSD; Travel grants: MSD, Astrazeneca, Roche, BMS; Speaker: Astrazeneca, MSD, Roche; Research grants: Astellas, Amgen-Roche, Astrazeneca, Boehringer Ingelheim, MSD. R.A. Soo: Honorarium, advisory board: AstraZeneca, BMS, Boehringer Ingelheim, Lilly, Merck, Novartis, Pfizer, Roche, Taiho; Research funding: Astra-Zeneca. T. Kozuki: Honoraria: Chugai, AZ, Lilly Japan, Pfizer, Ono Pharmaceutical, BMS Japan, Kyowa Hakko Kirin, Nippon BI, Nippon Kayaku, Taiho, MSD; Institution research funding: Chugai, AstraZeneca, Lilly Japan, Pfizer, Ono, BMS Japan, Merck Serono, M.R. Migliorino: Honoraria, consulting or advisory role: Astrazeneca, BMS, Pfizer, Roche. No relevant conflicts of interest for this work; my institution at any time don't receive payment or services from a third party (government, commercial, private foundation, etc.) for any aspect of the submitted work (including but not limited to grants, data monitoring board, study design, manuscript preparation, statistical analysis, etc.) W. Yu, S.W. Sun: Employee of Genentech/Roche. V. Graupner: Employee and shareholder: Roche. M. Kowanetz: Employee of Genentech/Roche; Stock: Roche. T. Hoang: Salary and stocks: Roche/Genentech. W. Lin: Employee: Genentech/Roche; stock: Roche. R.M. Jotte: Speaker's bureau, travel, accommodations, expenses, honoraria: BMS. All other authors have declared no conflicts of interest.

ObjectivesThe combination of pemetrexed and carboplatin is a standard first-line treatment for patients with advanced NSCLC. In this pilot phase II trial, we evaluated the feasibility of using pemetrexed and carboplatin as neoadjuvant therapy, prior to definitive surgical resection, for patients with localized NSCLC.Patients and methodsPatients with potentially resectable, previously untreated, clinical stage IB-III, nonsquamous NSCLC were eligible for this trial. All patients received 4 cycles of pemetrexed (500 mg/m2) and carboplatin (AUC 6.0) administered at 21 day intervals. Three to 6 weeks after completion of chemotherapy, definitive surgical resection was attempted. The primary endpoint of this trial was the 3-year survival rate.ResultsForty-six patients began protocol treatment, and 40 completed 4 courses of pemetrexed/carboplatin. Surgical resection was performed in 27 patients (59%); all had pathologic partial responses. The estimated 3-year survival rate for the entire group was 46%. Toxicity of neoadjuvant therapy was consistent with toxicity previously reported with pemetrexed/carboplatin.ConclusionsAdministration of 4 courses of pemetrexed/carboplatin was feasible. The efficacy was similar to neoadjuvant regimens previously investigated. A significant number of patients 19 of 46 (41%) in this trial did not have surgical resection after neoadjuvant therapy. Further investigation of the role of neoadjuvant pemetrexed/carboplatin requires a larger, randomized clinical trial.

Background: PD-1/PD-L1 inhibitors (PDx) improve survival in ≥ 2L NSCLC, primarily in PD-L1 high pts. Combining PDx with CTLA-4 agents may address unmet medical needs by providing synergistic antitumor activity even in PD-L1 low/neg pts in this setting. This Phase 3 trial (NCT02352948) evaluated durvalumab (D) vs SoC and D plus anti-CTLA-4 tremelimumab (T) vs SoC in Stage IIIB/IV NSCLC. Methods: Eligible pts had ≥2 prior systemic treatments (1 platinum-based CT), WHO PS 0/1, no prior PDx and were EGFR/ALK WT. From Q2 2015, in sub study A (SSA), PD-L1 TC ≥25% (Ventana SP263 assay) pts were randomized 1:1 to D 10 mg/kg IV q2w for up to 12 mo or SoC (erlotinib 150 mg QD PO, gemcitabine 1000 mg/m2 IV [day 1, 8, and 15 of a 28-day cycle] or vinorelbine 30 mg/m2 IV [day 1, 8, 15, and 22 of a 28-day cycle]). In sub study B (SSB), PD-L1 TC <25% pts were randomized 3:2:2:1 to D+T (D 20 mg/kg IV + T 1 mg/kg IV q4w for up to 12 wks then D 10 mg/kg IV q2w for 34 wks); SoC (as SSA); D (as SSA); or T 10 mg/kg IV q4w for 24 wks then q12w for 24 wks. Co-primary endpoints were OS and PFS for D+T vs SoC in SSB and D vs SoC in SSA. Secondary endpoints included 12-mo OS and PFS, ORR, safety and QoL. All 5% alpha was given to SSB (4% OS; 1% PFS); SSA was descriptive with no statistical testing. Results: Due to recruitment challenges 126/250 (SSA) and 469/600 (SSB) planned pts were randomized (DCO Feb 09 2018). Baseline characteristics were well balanced. In SSB, median OS was 11.5 vs 8.7 mo with D+T vs SoC (HR 0.80 [95% CI 0.61, 1.05]; p = 0.109). 12-mo OS rates were 49.5% and 38.8%. Median PFS was 3.5 vs 3.5 mo (HR 0.77 [0.59, 1.01]; p = 0.056) with 12-mo PFS rates of 20.6% and 8.0%. ORR was 14.9% D+T and 6.8% SoC. In SSA, median OS was 11.7 vs 6.8 mo with D vs SoC (HR 0.63 [0.42, 0.93]). 12-mo OS rates were 49.3% and 31.3%. Median PFS was 3.8 vs 2.2 mo (HR 0.71 [0.49, 1.04]) with 12-mo PFS rates of 19.4% and 9.9%. ORR was 35.5% D and 12.5% SoC. Grade ≥3 treatment-emergent AEs were 46.8% D+T and 54.5% SoC in SSB; 45.2% D and 66.7% SoC in SSA. Conclusions: In the ≥3L setting, D monotherapy provided a clinically meaningful improvement in OS vs SoC in PD-L1 TC ≥25% pts. D+T did not significantly improve OS or PFS vs SoC in PD-L1 TC <25% pts. D+T, D and T exhibited manageable safety profiles. Further biomarker analyses may help identify pts who may benefit most from D+T, D or T in advanced NSCLC. Clinical trial identification: NCT02352948/January 28, 2015. Editorial acknowledgement: Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Paul Glacken, MSc, and Elizabeth Andrew, PhD, of Cirrus Communications (Macclesfield, UK), an Ashfield company, and was funded by AstraZeneca. Legal entity responsible for the study: AstraZeneca. Funding: AstraZeneca. Disclosure: N. Reinmuth: Personal fees: BMS, Roche, AstraZeneca, Takeda, Novartis, Boehringer Ingelheim, MSD, Lilly. S. Sugawara: Lecture fees and research grant: AstraZeneca. D.M. Medine: Speaker and member of an advisory board: Roche; Advisory board: BMS, Boehringer Ingelheim. S. Novello: Speakers' bureau: Eli Lilly, Roche, BMS, Takeda, BI, AstraZeneca. Y. Takeda: Research funding: Taiho, Boehringer Ingelheim, Chugai, Kyowa Hakko Kirin. R.A. Soo: Honorarium and research funding: AstraZeneca; Honorarium: BMS, Boehringer Ingelheim, Lilly, Merck, Novartis, Pfizer, Celgene, Ignyta, Roche, Taiho. S.L. Geater: Non-financial support: Boehringer Ingelheim, AstraZeneca, Sanofi Aventis, Novartis; Grants: Boehringer Ingelheim, AstraZeneca, Novartis. M. Powell, R. May: Full-time employment: AstraZeneca. P. Stockman: Full-time employment and equity ownership: AstraZeneca. D. Planchard: Personal fees associated for advisory boards: AstraZeneca, Boehringer Ingelheim. BMS, MSD, Pfizer, Novartis, Roche, Celgene. All other authors have declared no conflicts of interest.

Background: Demonstrated benefit with maintenance therapy in patients (pts) with squamous NSCLC remains an unmet need. In a subset of pts with advanced squamous NSCLC from a large phase 3 trial, nab-P/C demonstrated a significantly higher improvement in the primary endpoint, overall response rate (ORR; 41% vs 24%; P < 0.001), vs P/C. The ABOUND.sqm study investigated induction nab-P/C followed by nab-P maintenance for these pts. Methods: Pts with treatment-naive, advanced squamous NSCLC received 4 cycles of induction nab-P 100 mg/m2 on d 1, 8, and 15 + C AUC 6 on d 1 (21-d cycles). Pts not progressing after 4 cycles were randomized 2:1 to maintenance nab-P 100 mg/m2 on d 1 and 8 of each 21-d cycle + best supportive care (BSC) or BSC alone until disease progression (PD) or unacceptable toxicity. Progression-free survival (PFS) from randomization into the maintenance part of the study was the primary endpoint. Secondary endpoints included safety, overall survival (OS), and ORR. Results: Of the 420 pts treated in the induction phase, 202 were randomized to maintenance nab-P + BSC (n = 136) or BSC alone (n = 66). In both arms, the median age was 68.0 yrs. All patients were followed for a minimum of 12 mos; median follow-up time for survival was 24.2 mos. PFS from randomization was not significantly different between nab-P + BSC and BSC alone (median, 3.1 vs 2.6 mos; P = 0.357); median OS was 17.6 and 12.2 mos, respectively. Additional efficacy outcomes are reported in the table. The most frequent grade 3/4 TEAEs over the entire study were neutropenia (53.1% vs 50.0%) and anemia (33.1% vs 32.3%). Conclusions: Induction nab-P/C followed by maintenance nab-P is feasible for pts with advanced squamous NSCLC. PFS from randomization with nab-P + BSC was not significantly longer vs BSC alone; however, OS was encouraging. No new safety concerns were identified during nab-P maintenance.Table: LBA64Efficacy outcomesOutcomenab-P + BSCBSC alonePFS (ITT population)n13666Median, months3.12.6HR (95% CI)0.85 (0.61 - 1.19)P value0.3571-year PFS rate, %1614OS (ITT population)n13666Median, months17.612.2HR0.72 (0.49 - 1.04)P value0.0761-year OS rate, %6650OS (ITT population, patients with subsequent immune checkpoint inhibitors)n8141Median, months18.815.5HR (95% CI)0.62 (0.39 - 0.99)P value0.044OS (ITT population, patients without subsequent immune checkpoint inhibitors)n5525Median, months12.97.6HR (95% CI)0.84 (0.46 - 1.54)P value0.575Response rate (ITT population)n13666ORR over entire study, %69.157.6RRR (95% CI)1.20 (0.95 - 1.52)P value0.087RRR, relative risk ratio. Open table in a new tab RRR, relative risk ratio. Clinical trial identification: NCT02027428. Legal entity responsible for the study: Celgene Corporation. Funding: Celgene Corporation. Disclosure: D.R. Spigel: Consulting/advisory role, Celgene; Research funding: Celgene; Travel, accommodations, expenses: Celgene. D. Morgensztern: Advisory board: Celgene, Bristol-Myers Squibb; Speaker’s bureau: Genentech. M.A. Socinski: Honoraria, speaker’s bureau: Celgene. O. Juan-Vidal: Advisory or speaker: AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Lilly, MSD, Pierre-Fabre, Pfizer, Roche. E.S. Kim: Grant/research support: Celgene. H.J. West: Consultant/advisor, honoraria: AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb, Celgene, Genentech/Roche, Merck, Spectrum, Takeda; Speaker: BMS, Genentech/Roche. T. Chen, R. Bhore, T.J. Ong: Employee of Celgene Corporation. M. Thomas: Honoraria, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Celgene, Lilly Novartis, MSD, Roche. All other authors have declared no conflicts of interest.

CheckMate 153 (NCT02066636) is an ongoing, predominantly community-based, phase 3B/4 safety study of nivolumab in patients with previously treated metastatic NSCLC in the US/Canada. Here we report safety, efficacy, and patient-reported outcome (PRO) data for subgroups of patients aged ≥70 years or with a poor baseline ECOG PS (PS2). Patients were enrolled in four subgroups based on histology and prior regimen number; one subgroup enrolled patients with squamous (SQ) or non-SQ NSCLC, PS2, and ≥1 prior therapies. Data on elderly patients were pooled across subgroups. The primary objective was assessment of high-grade (grade 3–4 and 5) select (those with a potential immunologic cause) treatment-related AE (TRAE) incidences. Exploratory endpoints included efficacy, biomarkers, pharmacokinetics, and PROs. Of 1,308 patients, 520 (40%) were aged ≥70 years and 108 (8%) had PS2. TRAE incidences for the age and PS subgroups were comparable with those for the overall population (table), as were select TRAE incidences for the subgroups. Estimated 6-month OS was lower with PS2 than PS0‒1, but similar between age subgroups and the overall population (table). Early PRO data revealed significant improvements overall in both age subgroups using LCSS and EQ-5D VAS, with younger patients showing greater improvement on some scales. Patients with SQ disease and PS2 generally reported stable quality-of-life/symptom control, whereas patients with non-SQ disease had statistically significant improvements on most scales. Updated data, including 1-year OS, will be presented. In this large study of advanced, previously treated, predominantly community-based patients with NSCLC, the nivolumab safety profile for age and PS subgroups was comparable with those for the overall population and from prior nivolumab NSCLC studies. OS was similar in younger and older patients, but lower in PS2 patients at early time points. Nivolumab appears to have similar risks/benefits in older and poorer PS patients as in the general population.

BACKGROUND:Longitudinal data on the impact of treatment on quality of life (QoL) in advanced non-small cell lung cancer (NSCLC) are limited. In this palliative setting, treatment that does not deteriorate QoL is key. Here we report longitudinal QoL in patients with squamous NSCLC, receiving ≤4 cycles of nab-paclitaxel/carboplatin combination chemotherapy.METHODS:Patients received nab-paclitaxel 100 mg/m2 days 1, 8, 15 + carboplatin area under the curve 6 mg•min/mL day 1 (q3w) for four cycles. QoL was assessed by the Lung Cancer Symptom Scale (LCSS) and Euro-QoL-5 Dimensions-5 Levels (EQ-5D-5L) at baseline and each cycle (day 1).RESULTS:Two-hundred and six lesion-response-evaluable patients completed baseline + ≥1 postbaseline QoL assessment and were QoL evaluable. LCSS average total score and symptom burden index improved from baseline throughout four cycles. In the LCSS pulmonary symptoms score, 46% of patients reported clinically meaningful improvement (≥10 mm visual analog scale) from baseline. Individual EQ-5D-5L dimensions remained stable/improved in ≥83% of patients; ≈33% reported complete resolution of baseline problems at least once during four cycles. Generally, responders (unconfirmed complete/partial response) had higher scores vs nonresponders.CONCLUSION:In patients with squamous NSCLC, four cycles of nab-paclitaxel/carboplatin demonstrated clinically meaningful QoL improvements, with greater benefits in responders vs nonresponders.

Background: Nivolumab, the anti-programmed death (PD)-1 antibody, has demonstrated durable responses and survival benefit in pts with advanced NSCLC, with some pts continuing to derive benefit even after discontinuation of nivolumab (due to adverse events [AEs] or a stopping rule). This raises the question of whether continuous nivolumab treatment is necessary for long-term benefit. CheckMate 153 (NCT02066636), an ongoing phase IIIB/IV study conducted primarily in the community setting, is evaluating the clinical benefit of a fixed-duration (1 yr) of nivolumab treatment vs continuous treatment in pts with previously treated advanced NSCLC. Pts who remained on nivolumab treatment for 1 yr were randomized to either continue receiving treatment or to stop treatment. Methods: Pts with stage IIIB/IV NSCLC and ≥1 prior systemic therapy were enrolled and treated with nivolumab 3 mg/kg IV Q2W. The primary objective of the study overall was the incidence of high-grade (grade 3–5) select treatment-related AEs. Pts still on treatment at 1 yr were randomized 1:1 either to continue nivolumab until progressive disease, unacceptable toxicity, or withdrawal of consent (continuous-treatment arm), or to discontinue treatment, with the possibility of resuming treatment upon disease progression (fixed-duration arm). Prespecified exploratory objectives included safety and efficacy in the 2 randomized arms. Results: As of April 2016, 1375 pts were enrolled and treated; 218 pts were randomized after 1 yr of treatment to the continuous-treatment arm (n = 111) or the fixed-duration arm (n = 107). Of these 218 pts, 133 (61%) had received ≥2 prior therapies and 10 (5%) had baseline ECOG PS 2. Data from an upcoming database lock (at which time, the expected post-randomization follow-up ≥10.7 mo) will be presented for randomized pts and will include overall survival, progression-free survival, and safety. In addition, data from pts who were re-treated in the fixed-duration arm will be presented. Conclusions: The results from CheckMate 153 represent the first insights from a randomized trial evaluating the impact of stopping treatment with a PD-1/PD-L1 inhibitor at 1 yr vs continuing treatment in pts with advanced, previously treated NSCLC. Clinical trial identification: NCT02066636 Legal entity responsible for the study: Bristol-Myers Squibb Funding: Bristol-Myers Squibb Disclosure: D.R. Spigel: Served as a consultant or advisor for Genentech/Roche (Inst), Novartis (Inst), Celgene (Inst), Bristol-Myers Squibb (Inst), Lilly (Inst), AstraZeneca (Inst), Pfizer (Inst), Clovis Oncology (Inst), Boehringer Ingelheim (Inst); travel funding from Genentech/Roche, Novartis, Celgene, Bristol-Myers Squibb, Lilly, AstraZeneca, Pfizer, Clovis Oncology, Biodesix, Boehringer Ingelheim, Peregrine Pharmaceuticals; owns stock in Foundation Medicine, Illumina; received institutional research funding from Genentech/Roche, Novartis, Celgene, Bristol-Myers Squibb, Lilly, AstraZeneca, Pfizer, Clovis Oncology, Boehringer Ingelheim, Peregrine Pharmaceuticals, Oncogenex, OncoMed, Amgen, Verastem, Daiichi Sankyo, University of Southwestern Medical Center – Simmons Cancer Center, Merck. D.M. Waterhouse: Served as consultant for BMS and Lilly; participated in speakers' bureau for BMS, Celgene, Genentech/Roche, and Lilly. L. Einhorn: Served as a consultant for Celgene and ZIOPHARM Oncology; owns stock or other ownership interests with Amgen and Biogen Idec. L. Horn: Served as consultant for BMS, Merck, Bayer, Xcovery, GNE, BI, and Lilly; received honoraria for Biodesix; institution received research funding for AstraZeneca. B. Creelan: Participated on a speakers' bureau for AstraZeneca and BMS; received research funding for Boehringer Ingelheim; travel funding from AstraZeneca, Merck Sharp & Dohme. S. Babu: Received research funding, consultancy fees, and travel honoraria from Alexion Pharmaceuticals. N.B. Leighl: Received honoraria from Pfizer; received institutional research funding from Novartis; travel funding from AstraZeneca and Merck, Sharp & Dohme. J. Chandler: Served as consultant for BMS; participated in speakers' bureau for Janssen; received research funding from BMS, EMD Serono, GNE/Roche, GSK, Lilly, and Onyx; travel funding from BMS and Janssen. G. Goss: Received honoraria from AZ, BI, BMS, Lilly, Pfizer; served as a consultant or advisor for AZ, BI, BMS; and received travel funding from AZ, BI, BMS, Pfizer. E.B. Garon: Institution received research funding from Merck, Genentech, AstraZeneca, Novartis, Pfizer, Lilly, Bristol-Myers Squibb, and Boehringer Ingelheim. A. Li, N. Aanur: Employed by BMS and owns stock in BMS. R. Jotte: Received honoraria from Bristol-Myers Squibb and Lilly; participated in speakers' bureau for Bristol-Myers Squibb and Lilly. All other authors have declared no conflicts of interest.

Background: The ABOUND.sqm trial is currently investigating treatment outcomes of 4 cycles of nab-P/C followed by nab-P maintenance therapy in patients (pts) with SCC NSCLC. Given that tolerability is an important consideration for treatment decisions, this analysis evaluated the safety of nab-P/C during induction. Methods: Chemotherapy-naive pts with stage IIIB/IV SCC NSCLC received 4 cycles of induction therapy with nab-P 100 mg/m2 d1, 8, and 15 + C area under the curve 6 d 1 (21-d cycles). Pts not progressing after induction received (2:1) maintenance nab-P 100 mg/m2 d1 and 8 (21-d cycles) + best supportive care (BSC) or BSC alone until progression/unacceptable toxicity. The primary endpoint is progression-free survival (randomization to maintenance). Secondary endpoints include safety analyzed as treatment-emergent adverse events (TEAEs), overall survival, overall response rate, and disease control rate. Results: A total of 334 pts were included in this analysis. Median age was 68 yrs; 90% were white, 68% male, and 68% had ECOG PS 1. During induction, 145/334 pts (43%) discontinued treatment. Of these, 51/145 (35%) discontinued due to progressive disease, 39/145 (27%) due to adverse events, 16/145 (11%) each due to death and pt withdrawal, 13/145 (9%) due to symptomatic deterioration, 9/145 (6%) due to other, and 1/145 (< 1%) due to protocol violation. The median percentage of per-protocol dose of nab-P was 74%; median nab-P dose intensity and cumulative dose were 74.08 mg/m2/week and 900 mg/m2, respectively. nab-P dose modifications included ≥ 1 reduction, missed dose, or dose delay in 55%, 60%, and 60% of pts, respectively. Grade ≥ 3 TEAEs were mainly hematologic and included neutropenia (148/334 [44%]), anemia (92/334 [28%]), and thrombocytopenia (48/334 [14%]). Grade ≥ 3 peripheral neuropathy was observed in 14/334 pts (4%). Conclusions: This interim analysis demonstrates the safety and tolerability of nab-P/C induction therapy in pts with SCC histology. The findings are consistent with those reported in subset analysis of the phase III study and provide additional support for the use of this regimen in this pt population. NCT02027428. Clinical trial identification: NCT02027428 Legal entity responsible for the study: Celgene Corporation Funding: Celgene Corporation Disclosure: C. Gridelli: Honoraria: Celgene. D. Morgensztern: Advisory role: Celgene; Speaker bureau: Boehringer. O. Juan: Advisory or Speaker role: Roche, Astra, MSD, Boehringer, BMS, Lilly, Pfizer, Pierre-Fabre. B. Levy: Honoraria: Eli Lilly, Genetech, Astra-Zeneca, Celgene; Consulting or Advisory Role: Eli Lilly, Genetech, Astra-Zeneca, Celgene; Speakers' Bureau: Eli Lilly, Genetech. A. Ardizzoni: Honoraria: Eli Lilly, BMS, MSD, Boehringer; Consulting Role: Eli Lilly, BMS, MSD, Boehringer. T. Berry: Employment and Stock Ownership: Celgene. T. Chen, N. Trunova: Employment and stock ownership: Celgene. All other authors have declared no conflicts of interest.