Osimertinib, a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor (TKI), is widely used as the first-line treatment for EGFR mutation-positive non-small cell lung cancer (NSCLC), but its efficacy and safety of osimertinib in real-world clinical practice remain to be fully elucidated in Japanese population. In addition, most cases ultimately acquire resistance to osimertinib, and no effective treatment has been currently established for cases having progressive disease (PD) with osimertinib.

Dual inhibition of the EGFR/VEGF pathways has demonstrated superior efficacy with 1st generation EGFR tyrosine kinase inhibitor (TKI) in patients with non small cell lung cancer (NSCLC) harboring EGFR mutations. This study aims to evaluate the efficacy and safety of combining osimertinib (Osi), a 3rd generation TKI considered the standard of care, with ramucirumab (Ram). Previously untreated patients with advanced NSCLC and EGFR mutations were randomized to receive Osi daily with or without Ram every 2 weeks. Eligibility included asymptomatic and/or treated brain metastases. Stratification was based on gender and mutation type (exon 19 del, L858R). The primary endpoint was progression free survival (PFS) assessed by central radiologic review. Between November 2018 and April 2020, 122 patients (Osi+Ram arm: 59, Osi arm: 63) were enrolled. With a median follow up of 36.0 months (m), median PFS was 20.0 m for Osi+Ram arm and 24.0 m for Osi arm, resulting in a hazard ratio of 1.054 (95% CI 0.674-1.648, p = 0.82). The overall response rate was 77.2% and 79.3%, with a median duration of response of 24.7 m and 25.1 m in the Osi+Ram and Osi arms respectively. Notable grade 3 or higher adverse events (≥10%) included CK elevation (13%) in Osi arm, neutropenia (10%) and hypertension (17%) in Osi+Ram arm. Pneumonitis of any grade occurred in 9% and 16% of Osi+Ram and Osi arms. Median treatment durations for Osi and Ram were 18.8 (0.5-49.7) and 4.6 (0.5-40.7) m in the Osi+Ram arm, and 17.4 m in the Osi arm. The treatment period of Ram was shorter compared to previous studies. In a post hoc analysis, PFS favored the Osi+Ram combination among patients with brain metastasis (n=34) with a hazard ratio of 0.655 (95% CI 0.296-1.451). While both treatment arms demonstrated long-term effects with acceptable toxicity, this study did not reveal an advantage of the Osi+Ram combination over Osi monotherapy in improving PFS. It's noteworthy that conducted period during the COVID-19 pandemic, and the suboptimal administration of Ram may have influenced the outcome. jRCT2080224085

Pembrolizumab (Pemb) is a key drug for the treatment of advanced or recurrent non-small cell lung cancer (NSCLC). However, there are limited data on Pemb use in older adults aged >75 years with NSCLC, especially in terms of pharmacokinetics (PK). This open-label multicenter observational study aimed to evaluate real-world data on the safety, efficacy, and blood concentrations of Pemb (both monotherapy and combination therapies) in older adults with NSCLC. Blood samples for PK analysis were collected immediately before Pemb administration. Quantitative Pemb concentrations were measured by liquid chromatography-mass spectrometry. We enrolled 100 patients from July 2019 to September 2020; one patient was excluded due to stage migration. Patient characteristics were as follows: median age, 78 (75–87) years; male/female ratio, 70/29; performance status (PS) 0–1/2–3, 85/14; adenocarcinoma/squamous cell carcinoma/others, 62/25/12; stage I–III/IV/postoperative recurrence (TNM 7th edition), 9/60/30; PD-L1 TPS <1%/1%–49%/≥50%, 12/31/48; and monotherapy/combination therapy, 65/34. The best overall efficacy was CR/PR/SD/PD (7/40/32/20), and the response rate was 47.5%. The median progression-free survival (PFS) and overall survival (OS) were 8.0 and 19.0 months, respectively. The adverse event profile was generally similar to that reported in previous studies. In total, 77 blood samples were collected immediately before the second cycle (C1 trough). Although no clear association between Pemb concentrations and patient background was found, PFS and OS were significantly shortened in the population with low C1 trough, a population characterized by lower PS, high number of metastatic organs at the beginning of treatment, and low blood albumin level. In older adults aged >75 years with NSCLC and low albumin levels and PS and a high number of metastatic organs, C1 trough of Pemb is reduced and not expected to prolong PFS and OS.

Biomarker for the combination of chemotherapy and immune checkpoint inhibitor in extensive-stage small-cell lung cancer have not been identified at this time, and neither TC expression, IC expression, nor tTMB expression have been significant biomarkers in exploratory PD-L1 analysis of the CASPIAN study. Early identification of factors that would allow for long-term treatment duration of the durvalumab plus platinum-etoposide regimen is very important, and we focused on the best reduction from baseline in target lesion size.

In patients with NSCLC harboring molecular alterations, the efficacy of immune checkpoint inhibitors (ICI) remains unknown. The aim of our study was to examine the efficacy of first-line ICI among patients having NSCLC with KRAS, MET, FGFR, RET, BRAF, and HER2 alterations, compared to those with driver-unknown.

Osimertinib is one of the standard treatments for the patients with EGFR mutated lung cancer. Osimertinib showed a statistically significant difference in PFS and OS when compared to first-generation EGFR-TKI. However, predictors of efficacy and safety are still unknown. At this time, we evaluated the relationship between plasma osimertinib concentrations and treatment results.

Osimertinib is now available not only as a second line treatment for the patients with EGFR and T790M-mutation positive non-small cell lung cancer (NSCLC) after initial tyrosine kinase inhibitors (TKIs) but as a first line treatment for those who are TKI-naive. However, the efficacy as well as safety of osimertinib plus palatinum-based chemotherapy has not yet been evaluated.

Objective: Adjuvant chemotherapy is standard of care for patients with completely resected stage IB, II and IIIA NSCLC. However, optimum chemotherapy regimen has not been determined. TORG0503 was undertaken to select a preferred platinum-based 3rd generation regimen in this clinical setting. Materials and methods: Patients with completely resected stage IB, IIA, LIB or stage IIIA NSCLC were stratified by stage (IB/IIA vs. IIB/IIIA) and institutions, and randomized to receive 3 cycles of docetaxel (60 mg/m(2)) plus cisplatin (80 mg/m2) (arm A) or paclitaxel (200 mg/m(2)) plus carboplatin (AUC 6) (arm B) on day 1, every 3 weeks. The primary endpoint of the study was 2-year relapse free survival, and the key secondary endpoints included overall survival, feasibility and toxicity. Results: 111 patients were randomized, 58 patients to arm A and 53 to arm B. Patient demographics were balanced between the two arms. 93 % (54/58) of patients on the arm A and 92 % (49/53) patients on the arm B completed the planned 3 cycles of chemotherapy. There was no treatment-related death in both arms. The 2 and 5 year relapse free survival was 74.5 % (95 %CI: 68.6-80.4) and 61.6 % in the arm A, and 72.0 % (95 %CI: 65.7-78.3) and 46.0 % in the arm B. The overall 2, 5-year survival was 89.7 %, 73.9 % in the arm A and 86.9 %, 67.5 % in the arm B. Conclusion: Both docetaxel plus cisplatin and paclitaxel plus carboplatin are safe and feasible regimens as adjuvant chemotherapy. We choose docetaxel plus cisplatin as the control regimen for the next clinical trial.

Although reports on the use of gefitinib or erlotinib in elderly patients were occasionally found, those on afatinib were rare. According to the analysis of 54 Japanese patients in the LUX-Lung3 study, the dose reduction of afatinib from 40 mg/day was necessary for 76.0% of patients. However, the prolonged administration was possible after a dose reduction to 30 or 20 mg/day, and antitumor effects were maintained with the reduced dose. The efficacy and safety of afatinib at 30 mg/day in PS 0-1 patients who were aged 75 years with EGFR mutation positive chemotherapy-naïve non-small cell lung cancer were studied. The primary endpoint was the response rate (RR), and the planned number of registered cases was set at 35, with a threshold RR of 50%, an expected RR of 75%, α of 0.05, and β of 0.1. The secondary endpoints were progression-free survival (PFS), overall survival (OS), the incidence rate of adverse events (AEs), QOL survey (FACT-L), and trough plasma concentration of afatinib at steady state (PK, collected between the 8th to 15th day after the start of oral administration). The data of 35 patients were collected from May 2015 to August 2017. Patient background was, median age of 79 years (75-92), male/female: 8/27, PS 0/1: 8/27, adenocarcinoma/NSCLC: 30/5, IIIA/IIIB/IV/postoperative recurrence (TNM 7th edition): 2/2/22/9, and exon19del/exon21L858R/exon19del+exon21L858R: 15/19/1. The best overall efficacy was PR/SD/PD/NE: 28/4/1/2, and the RR was 80.0% (95% CI, 63.1-91.6). The median PFS and OS were 16.3 months (95% CI, 11.8-27.0) and not reached, respectively. The main AEs were rash 69%, diarrhea 60%, and paronychia 51%. While the initial afatinib dose was 30 mg, nine (26%) patients continued with 30 mg, 23 (66%) were reduced to 20 mg, and 3 (8%) discontinued due to AEs (2 ILD and 1 stomatitis). Treatment-related death was not observed. There were no significant change of QOL at baseline, after 4, 8, and 12 weeks. PK analyses showed steady state plasma concentration as 22.8 ng/mL which was comparable to reported plasma concentration of 40 mg afatinib in LUX-LUNG3 and 6 (24.3 ng/mL). No obvious PK differences were found according to dose reduction, adverse event, and response. Afatinib at 30 mg/day could be an effective treatment option for elderly patients, over 75 years of age, with good PS. (UMIN 0000177050)

EGFR mutation analysis of plasma circulating tumor DNA (ctDNA) has been reported to be useful to detect resistant mutations and to predict the efficacy of treatment. In NEJ026 study, we demonstrated the PFS of erlotinib plus bevacizumab (BE) treatment was significantly superior to the erlotinib alone (E) in NSCLC patients harboring EGFR mutation. Evaluation of plasma EGFR mutations included in NEJ026 study as preplanned analysis. At the time points of pretreated (P0), 6 weeks after study treatment started (P1), and confirmed progressive disease (P2), the plasma samples were collected from the patients enrolled to NEJ026 study. The number of enrolled patients were 112 in BE and 114 in E. Plasma ctDNA analysis for detection of the activating EGFR mutation and T790M mutation were performed by modified PNA-LNA PCR clamp method. The total numbers of collected plasma samples in BE and E were 108 (96.4%) and 107 (95.5%) at P0, 95 (84.8%) and 97 (86.6%) at P1, and 42 (37.5%) and 53 (47.3%) at P2, respectively. In eligible patients having EGFR activating mutation detected by cytohistological specimens, detection rate of plasma EGFR mutation at P0 was 68% (147/215). The detection ratio of T790M mutation at P2 were similar in both arms: 8 (19.0%) in BE and 11 (20.8%) in E. By detection pattern of activating EGFR mutation, PFS was evaluated among three groups: type A (P0 (-), P1 (-)), type B (P0 (+), P1(-)), and type C (P0 (+), P1(+)). Type A achieved the best response to both TKI [Type A BE: 18.1 M (n = 32, 95% CI, 11.5 to upper limit not reached (NR)), E: 16.7 M (n = 26, 95% CI, 11.2 to NR )]. Type B also had better PFS to TKI and BE is more favorable effect than E compared to other types [type B BE: 15.5 M (n = 48, 95% CI, 12.4 to 23.3), E: 11.1 M (n = 57, 95% CI, 8.5 to 13.7)]. Type C showed worse response to both treatment [type C BE: 6.0M. (n = 12, 95% CI 2.6 to NR), E: 4.3 M (n = 10, 95% CI, 2.8 to 20.2)]. BE had better PFS in all types. Frequency of T790M in P2 was similar among BE and E. When patients still had detectable activating EGFR mutation in plasma ctDNA after treatment for 6 weeks, you should consider that they might have poor response to both BE and E.

C. T. Ke,1,* A. W. Draelos,1,* A. Seredinski,1,* M. T. Wei,1 H. Li,2 M. Hernandez-Rivera,2 K. Watanabe,3 T. Taniguchi,3 M. Yamamoto,4 S. Tarucha,4 Y. Bomze,1 I. V. Borzenets ,5,† F. Amet,2 and G. Finkelstein1 1Department of Physics, Duke University, Durham, North Carolina 27708, USA 2Department of Physics and Astronomy, Appalachian State University, Boone, North Carolina 28607, USA 3Advanced Materials Laboratory, National Institute for Materials Science, 1-1 Namiki, Tsukuba 305-0044, Japan 4Center for Emergent Matter Science (CEMS), RIKEN, Wako-shi, Saitama 351-0198, Japan 5Department of Physics, City University of Hong Kong, Kowloon, Hong Kong SAR

Background Although anti-PD-1 antibodies are the most promising agents in advanced non-small cell lung cancer (NSCLC), no definitive biomarkers of efficacy exist. We developed a novel assay for peripheral blood mononuclear cell (PBMC) biomarker using the prediction formula consisting of CD62L-downregulated (CD62Llow) CD4+T cells and CD25+Foxp3+CD4+T cells. This study aimed to validate it. Methods This prospective multicenter phase II study included patients with treated advanced or metastatic NSCLC. After registration and PBMC biomarker analysis, they were classified into responder (RT) or non-responder (NRT) type. Nivolumab was administered every two weeks. The primary endpoint was disease control rate (DCR) at nine weeks after nivolumab treatment in RT patients. Desired and threshold DCR were set at 80% and 60%, respectively. Secondary endpoints were objective response rate (ORR), time to treatment failure, progression-free survival (PFS), overall survival, safety and tolerability, comparison with NRT patients, and PBMC biomarker quality improvement. Results Of the 96 enrolled patients, 95 were eligible for PBMC analysis: 3 were unanalyzable, and 92 were analyzed; however, 40 had a minimal number of live cells. We excluded 19 patients who did not receive nivolumab in NRT and 1 with indeterminable treatment effect at nine weeks, and 72 patients comprised the per protocol set (PPS), of which 43 were RT and 29 NRT. The DCR and ORR in RT patients were 65.1% (95% confidence interval [CI], 50.9-79.4%) and 14.0% (95% CI, 3.6-24.3%), respectively. The PFS in RT patients was 113 days (95% CI, 65-158). As a subset analysis, we examined 45 patients (25 RT and 20 NRT) excluding those with ≥50% dead cell ratio in lymphocyte culture. The DCR was 80.0% (95%CI, 64.3-95.7) in RT and 50.0% (95% CI, 28.1-71.9) in NRT (chi-square test, p = 0.034). Conclusions In alive PBMC analysis, DCR was better in the RT than in the NRT patients. This PBMC biomarker using the ratio of CD62LlowCD4+T cells to CD25+Foxp3+CD4+T cells might be promising for predicting nivolumab efficacy. Clinical trial identification UMIN ID: UMI28468. Legal entity responsible for the study North East Japan Study Group (NEJSG). Funding Ono Pharmaceutical Co., Ltd., Bristol-Myers Squibb K.K. Disclosure O. Yamaguchi: Research grant / Funding (institution): Nihon Medi-Physics Co., Ltd.; Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Ono Pharmaceutical; Speaker Bureau / Expert testimony: Bristol-Myers Squibb. T. Kozuki: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self): Nippon Beohringer Ingelheim Co.; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb; Honoraria (self), Research grant / Funding (institution): Chugai Pharmaceutical Co.; Honoraria (self): Kyowa-Hakko Kirin; Honoraria (self), Research grant / Funding (institution): Eli Lilly Japan; Research grant / Funding (institution): Merck Biopharm; Honoraria (self): MSD; Honoraria (self): Ono Pharmaceutical Co.; Honoraria (self): Pfizer; Honoraria (self): Taiho Pharmaceutical Co. N. Furuya: Honoraria (self): Bristol-Myers Squibb; Honoraria (self): Lilly; Honoraria (self): Chugai Pharma ; Honoraria (self): AstraZeneca; Honoraria (self): Pfizer; Honoraria (self): Taiho Pharmaceutical; Honoraria (self): Ono Pharmaceutical. T. Yamada: Research grant / Funding (self): Ono Pharmaceutical Co., Ltd.; Research grant / Funding (self): Boehringer Ingelheim Japan Inc.; Research grant / Funding (self): Takeda Pharmaceutical Co. Ltd.; Research grant / Funding (self): Chugai Pharmaceutical Co., Ltd. R. Ko: Honoraria (self): Ono Pharmaceutical Co., Ltd. T. Harada: Honoraria (institution): Boehringer Ingelheim; Honoraria (institution): Hisamitsu Pharmaceutical Co., Inc; Honoraria (institution): GlaxoSmithKleine K.K. M. Seike: Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Bristol-Myers Squibb. K. Yoshimura: Honoraria (self): Chugai Pharma. K. Kobayashi: Speaker Bureau / Expert testimony: AstraZeneca; Speaker Bureau / Expert testimony: Boehringer Ingelheim; Speaker Bureau / Expert testimony: Taiho Pharmaceutical Company; Speaker Bureau / Expert testimony: Ono Pharmaceutical Company. H. Kagamu: Honoraria (self), Research grant / Funding (institution): Ono Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Taiho Pharmaceutical; Honoraria (self), Research grant / Funding (institution): Chugai Pharmaceutical; Honoraria (self): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Boehringer Ingelheim; Honoraria (self), Research grant / Funding (institution): Eli Lilly Japan. All other authors have declared no conflicts of interest.

Background: This single-center phase II study aimed to examine the efficacy and feasibility of nivolumab for patients with advanced non-small cell lung cancer (NSCLC) who were unsuitable for single-agent chemotherapy or targeted agents because of their poor performance status (PS). Methods: In this study, we enrolled previously treated patients with advanced NSCLC with poor PS of 2–4 without any indication of cytotoxic chemotherapy or targeted therapies. All enrolled patients received nivolumab (3 mg/kg, every 2 weeks) until progression or unacceptable toxicities. In addition, we prospectively obtained peripheral blood mononuclear cells (PBMC) and plasma from patients after obtaining their informed consent before treatment. Results: Between April 2016 and December 2017, we enrolled 33 patients with NSCLC and poor PS, including 23 patients with PS 3–4. In this study, the response rate was 29.0% (90% confidence interval (CI), 17.7%–43.7%), and the disease control rate was 41.9% in 31 evaluable patients. PS improvement rate was 29.0%. In addition, the median progression-free survival (mPFS), median overall survival (mOS), and 1-year survival rates were 1.5 (95% CI, 1.0–2.7) months, 3.8 (95% CI, 2.4–16.3) months, and 37.6%, respectively. Among patients harboring EGFR-mutations (mut), the mPFS was 2.6 and 1.1 months in EGFR-wild type (wt) and EGFR-mut (p = 0.015), respectively, and the mOS was 9.3 and 1.9 months in EGFR-wt and EGFR-mut (p = 0.029), respectively. During the study period, treatment-related deaths were observed in 2 patients (6.1%). We obtained blood samples from 75% of the enrolled patients (data will be updated in the meeting). Conclusions: To the best of our knowledge, this is the first trial to investigate the efficacy of immune checkpoints in patients with advanced NSCLC with poor PS. Although the response rate was similar to those with good PS, shorter survival was observed. Excluding patients harboring driver mutations may enhance treatment efficacy to show a survival benefit even for poor PS patients. Nevertheless, the biomarker investigation warrants focus on the PBMC analysis. Clinical trial identification: Clinical trial registration: UMIN000020855/UMIN000021734. Legal entity responsible for the study: Tokyo Metropolitan Komagome Hospital. Funding: Has not received any funding. Disclosure: Y. Okuma: Research Funding: Chugai Pharma (Inst). Y. Hosomi: Honoraria: AstraZeneca; Boehringer Ingelheim Japan; Bristol-Myers Squibb Japan; Chugai Pharma; Eli Lilly Japan; Ono Pharmaceutical; Taiho Pharmaceutical; Research Funding: Chugai Pharma (Inst); Eli Lilly Japan (Inst); Ono Pharmaceutical. N. Yamamoto: Honoraria: AstraZeneca; Bristol-Myers Squibb Japan, Chugai Pharma, Eli Lilly Japan, Ono Pharmaceutical, Pfizer; Research Funding: Astellas Pharma (Inst), Bayer (Inst), Boehringer Ingelheim (Inst), Chugai Pharma (Inst), Daiichi Sankyo (Inst), Eisai (Inst), Kyowa Hakko Kirin (Inst), Eli Lilly Japan (Inst), Novartis (Inst), Pfizer (Inst), Quintiles (Inst), Taiho Pharmaceutical (Inst), Takeda (Inst). All other authors have declared no conflicts of interest.

Background: Although reports on the use of gefitinib and erlotinib in elderly patients are occasionally found, reports on afatinib are rare. According to the analysis of Japanese patients in the LUX-Lung3 study, a dose reduction, from an initial dose of 40 mg/day, was necessary in 76.0% of the 54 patients in the afatinib group. However, prolonged administration was possible after dose reduction to 20 mg/day, and antitumor effects were maintained with the reduced dose. Methods: The efficacy and safety of afatinib at 30 mg/day in PS0-1 patients who were over 75 years of age with EGFR mutation positive non-small cell lung cancer were studied. The primary endpoint was the response rate, and the planned number of registered cases was set at 35, with a threshold response rate of 50%, expected response rate of 75%, α of 0.05, and β of 0.1. The secondary endpoints were progression-free survival (PFS), overall survival (OS), incidence rate of adverse events (AE), quality of life (QOL) survey, and trough plasma concentration of afatinib at steady state (PK, collected between 8th to 15th day of oral administration). Results: The data of 35 patients were collected from May 2015 to August 2017. Patient background was, median age of 79 years (75-92), male/female: 8/27, PS 0/1: 8/27, adenocarcinoma/non-small cell cancer: 30/5, IIIA/IIIB/IV/postoperative recurrence (TNM 7th edition): 2/2/22/9, and exon19del/exon21L858R/exon19del+exon21L858R: 15/19/1. The best overall efficacy was PR/SD/PD/NE: 28/4/1/2, and the response rate was 80.0% (95% CI, 63.1-91.6). The median PFS was 14.0 months (95% CI, 11.8-22.4). The main AEs were rash 69%, diarrhea 60%, paronychia 51%, stomatitis 49%, anemia 37%, loss of appetite 23%, thrombocytopenia 23%, and fatigue 20%. While the treatments were initiated with afatinib at 30 mg, nine (26%) patients continued with 30 mg, 23 (66%) were reduced to 20 mg, and three (8%) discontinued treatment due to AEs (2 cases of drug-induced pneumonia and 1 of stomatitis). Treatment-related death was not observed. Conclusions: Afatinib at 30 mg/day could be an effective treatment option for elderly patients, over 75 years of age, with good PS. This study also reported OS, PK, and QOL in detail. (UMIN 0000177050). Legal entity responsible for the study: Hokkaido University. Funding: Boehringer Ingelheim, AMED16ck0106112h003. Disclosure: Y. Nakahara: Honoraria: AstraZeneca, Eli Lilly, Bristol-Myers Squibb, Ono Pharmaceutical, Taiho; Pharmaceutical research funding: Eli Lilly. S. Oizumi: Honoraria: AstraZeneca, Eli Lilly; Research funding: Bristol-Myers Squibb, Kyowa Hakko Kirin, Merck Serono, Ono Pharmaceutical, Pfizer. H. Mizugaki: Honoraria: AstraZeneca, Boehringer Ingelheim, MSD, Chugai Pharmaceutical; Research funding: Boehringer Ingelheim. All other authors have declared no conflicts of interest.

Background: Although EGFR-TKI alone has been a standard first-line treatment for pts with advanced NSCLC with EGFR mutations, our phase II study (NEJ005) showed promising efficacy of GCP. NEJ009, an open-label, randomized phase III study, was conducted to evaluate the superiority of GCP vs G in progression-free survival (PFS), PFS2, and overall survival (OS). Methods: Pts with newly diagnosed stage III/IV/recurrent NSCLC harboring EGFR activating mutations (exon 19 deletion or exon 21 L858R) were randomized 1:1 to G 250 mg PO QD or GCP (G 250mg PO QD combined with carboplatin AUC 5 + pemetrexed 500mg/m2, every 3 weeks). The primary endpoints consisting of PFS, PFS2, and OS were sequentially analyzed according to a preplanned gate-keeping method. Secondary endpoints included objective response rate, safety, and quality of life. Results: From Oct 2011 to Sep 215, 345 pts were enrolled and 342 pts (G 172, GCP 170) were evaluated. Baseline characteristics fairly well balanced between the arms. GCP demonstrated significantly better PFS compared to G as below. Although there was no difference in PFS2 between the arms, additional OS analysis (G 101 events vs GCP 83 events) revealed that median survival time of GCP was much longer than that of G (52.2 months vs 38.8 months, HR: 0.695, p = 0.013). Details of post-protocol treatments in both arms will be presented at the meeting. Conclusions: NEJ009 was the first phase III study which evaluated the efficacy of a combination of EGFR-TKI and platinum doublet chemotherapy in untreated advanced NSCLC pts with EGFR mutations. Although GCP regimen failed to demonstrate its superiority in PFS2, it increased long survivors.Table: 1382PDITT populationGCP (N = 169)G (N = 172)Median (months)Median (months)HRPFS20.911.20.49395%CI:18.0, 24.295%CI:9.0,13.495%CI:0.390, 0.623P < 0.001PFS220.921.10.89195%CI:18.0,24.295%CI:17.9,24.995%CI: 0.708,1.122P = 0.806OS (additional analysis)52.238.80.695 (P = 0.013) Open table in a new tab Legal entity responsible for the study: North East Japan Study Group (NEJ). Funding: Has not received any funding. Disclosure: M. Seike: Lecture fees: AstraZeneca, Eli Lilly, Taiho Pharmaceutical. A. Inoue: Lecture fees: AstraZeneca, Eli Lilly, Boehringer Ingelheim, MSD, Chugai, Pfizer. S. Sugawara: Lecture fees: AstraZeneca, Chugai Pharma, Nippon Boehringer Ingelheim, Taiho Pharmaceutical, Pfizer, Eli Lilly and Company, Novartis, Kyowa Hakko Kirin, Bristol-Myers Squibb, Ono Pharmaceutical, MSD K.K. S. Morita: Lecture fees: AstraZeneca, Eli Lilly. Y. Hosomi: Lecture fees: AstraZeneca, Taiho Pharmaceutical, Lilly, Chugai Phama, Ono Taiho Pharmaceutical, Bristol-Myers Squibb Japan, MSD. K. Takahashi: Lecture fees and research funding: AstraZeneca, Eli Lilly. Y. Fujita: Lecture fees: Chugai, Ono, Eli Lilly; Research funding: Taiho, Chugai, Eli Lilly, Pfizer Japan. K. Minato: Research funding: Taiho, Bristol-Myers Squibb, Quintiles. K. Kobayashi: Lecture fees: AstraZeneca, Chugai, Ono, Eli Lilly; Consulting or advisory role fee: AstraZeneca. T. Nukiwa: Lecture fees: Asahi-Kasei, Nippon Boehringer Ingelheim. All other authors have declared no conflicts of interest.

Objectives: The TORG0809 study was a multicenter feasibility study of long-term single-agent therapy with S-1 after docetaxel plus cisplatin therapy in patients with completely resected stage II or stage IIIA non–small cell lung cancer. We report the results of the final overall survival (OS) analysis. Patients and Methods: A total of 129 eligible patients received 3 cycles of docetaxel (60 mg/m2, day 1) plus cisplatin (80 mg/m2, day 1), followed by S-1 at 40 mg/m2 twice daily for 14 consecutive days, for >6 months (maximum, 1 y). Results: At the cutoff date of April 13, 2016, the median follow-up time was 6.0 years. Of the 129 patients, 43 had died, and 74 patients developed disease recurrence or died. The median OS had not been reached. The 5-year OS rate was 71% [95% confidence interval (CI), 62-78]. The 5-year OS rates in the patients with stage II and stage IIIA were 76% and 68%, respectively. The median recurrence-free survival (RFS) duration was 3.4 years (95% CI, 2.3-5.7). The 5-year RFS rate was 44% (95% CI, 36-53). The 5-year RFS rates in patients with stage II and stage IIIA disease were 57% and 38%, respectively. Disease recurrence occurred in 68 patients, and 62 of these patients received second-line chemotherapy. The most common sites of recurrence were the brain (n=22) and mediastinal lymph nodes (n=22). Conclusion: The survival data obtained from this study are promising and comparable to those reported from a previous study conducted in Japan.

Background: About 5% of NSCLCs have high level of overexpression and/or amplification of HER2 or its mutations, mostly exon 20 insertions. Retrospective studies suggest some activity of a Her2-targeted antibody, trastuzumab, for HER2-altered NSCLCs. However, no clinical trial data of trastuzumab monotherapy for HER2-altered NSCLCs are available so far. Methods: HOT1303-B was a multicenter, single-arm phase II study of trastuzumab for NSCLC patients who were pretreated with two or more regimens and had HER2-altered tumors (IHC 3+ or IHC 2+/dual color in situ hybridization [DISH] +, and/or presence of mutations) identified by a HER2 screening study HOT1303-A and a nationwide genomic screening study LC-SCRUM-Japan. Eligible patients (pts) were treated with trastuzumab 6 mg/kg every 3 weeks (loading dose 8 mg/kg). The primary endpoint was the overall response rate (ORR) using RECIST v1.1. This study required ten pts, with ORR of 10% considered non-promising and 40% promising (one-sided alpha = 0.10; beta = 0.2). Results: Ten pts were recruited in this trial. The median age was 59 (range 44-74), three pts were female, three pts were never smokers, nine pts had performance status 0-1, and all had adenocarcinomas. The median lines of prior systemic therapy were 3 (range 2-6). There were two pts with IHC 3+, one pt with IHC 2+/DISH +, five pts with exon 20 insertions (four A755_G776insYVMA and one G776>VC) and two pts with S310F mutations without overlapping cases. ORR was 0% (95% CI, 0-26%). Disease control ratio (DCR) was 70% (95% CI, 39-91%). Median progression-free survival was 5.2 months (95% CI, 1.4-6.3). Grade ≥ 3 adverse events occurred only in a patient with grade 3 pneumonitis, which was judged as organizing pneumonia related with tumor progression. OS data will be presented at the meeting. Conclusions: Trastuzumab monotherapy did not produce response for HER2-altered NSCLCs in this cohort, although DCR and PFS seemed favorable for the heavily treated pts. Additional approaches including combination therapy are required for HER2-targeted therapy using trastuzumab. Clinical trial identification: UMIN000012551. Legal entity responsible for the study: Hirotoshi Dosaka-Akita. Funding: Ministry of Health, Labor and Welfare, Japan. Disclosure: I. Kinoshita: Honoraria: Chugai Phama, Novartis. M. Maemondo: Advisory role: Chugai Pharma, AstraZeneca, Boehringer Ingelheim, MSD, Bristol-Myers Squibb Japan, Ono Pharmaceutical, Pfizer, Novartis, Taiho Pharmaceutical, Lilly Japan; Research funding: Boehringer Ingelheim, Chugai Pharma, AstraZeneca, Novartis, Sanofi, MSD, Lilly Japan. S. Oizumi: Honoraria: AstraZeneca Japan, Lilly Japan; Research funding: Kyowa Hakko Kirin, Pfizer, BMS UK, Ono Pharmaceuticals. Y. Hatanaka: Advisory role: GeneticLab, Medicinal Chemistry Pharmaceutical Co.; Speakers' bureau: Merck Sharp & Dohme, Chugai Pharma, Pfizer; Honoraria: Ono Pharmaceutical, AstraZeneca KK.; Research funding: Roche, Taiho Pharmaceutical, Eisai, Merck Sharp & Dohme. T. Harada: Honoraria: Taiho Pharmaceutical, AstraZenea KK, Boehringer Ingelheim, Hisamitsu Pharmaceutical. K. Goto: Advisory role: Otsuka; Honoraria: Daiichi Sankyo, Bristol-Myers Squibb, AstraZeneca, Pfizer, Chugai Pharma, Taiho Pharmaceutical, Ono Pharmaceutical, Ono Pharmaceutical, Novartis, Lilly, Boehringer Ingelheim, Quintiles, Merck Serono, SRL Diagnostics, Life Technologies, F. Hoffmann La Roche AG, MSD, AbbVie, RIKEN GENESIS, Nippon Kayaku; Research funding: MSD, AstraZeneca, Taiho Pharmaceutical, Chugai Pharma, Boehringer Ingelhiem, Ono Pharmaceutical, OxOnc, Sumitomo Dainippon, Takeda, Novartis, Daiichi Sankyo, Kyowa Hakko Kirin, Astellas Pharma, Eisai, Lilly, Pfizer, Riken Genesisi, Bristol-Myers Squibb, Merck Serono, Abbvie, Ignyta. H. Isobe: Speakers' Bureau: Chugai Pharma, Bristol-Myers Squibb Japan, Pfizer. All other authors have declared no conflicts of interest.