8599 Background: EVOKE-01 (NCT05089734) assessed the efficacy and safety of SG vs docetaxel in pts with mNSCLC that progressed after platinum-based chemotherapy and anti–PD-(L)1 (IO) treatment. The study did not meet statistical significance for overall survival (OS) at final analysis. Here, we report updated survival and safety outcomes after longer follow-up, providing insight into the tolerability of SG over a prolonged period of administration. Methods: Pts were randomized 1:1 to receive SG (n = 299; 10 mg/kg IV, days 1 and 8) or docetaxel (n = 304; 75 mg/m 2 IV, day 1) in 21-day cycles until progression or unacceptable toxicity. OS was the primary endpoint, while safety was a key secondary endpoint. Results: As of Oct 21, 2024, median follow-up was 23.5 months. Median exposure with SG vs docetaxel was 3.5 vs 2.3 months; 33.4% vs 17.7% of pts, respectively, were exposed to study drug for ≥6 months. The longer follow-up preserved the numerical improvement in OS favoring SG in the intent-to-treat population (HR 0.89, 95% CI: 0.74–1.07; P = .1028) and in subgroups of interest, including nonresponders to prior IO, and across squamous and nonsquamous histologies ( Table ). Most common any-grade treatment-emergent adverse events (TEAEs) with SG vs docetaxel were fatigue (57.8% vs 56.6%), diarrhea (52.7% vs 33.7%), and alopecia (43.6% vs 30.2%). In line with the primary analysis, 68.6% vs 76.0% of pts receiving SG vs docetaxel experienced grade ≥3 TEAEs, mainly neutropenia (25.3% vs 36.8%), fatigue (12.5% vs 9.7%), and diarrhea (10.5% vs 3.8%). Discontinuations due to TRAEs were seen in 7.4% vs 14.2% of pts receiving SG vs docetaxel. There were no additional AEs leading to death reported with longer follow-up (Table). Conclusions: Consistent with the final analysis, SG showed a numerical improvement in OS vs docetaxel. Long-term safety showed SG is well tolerated, consistent with minimal increase in AE rates since prior report and an improved safety profile over docetaxel, despite longer treatment exposure. Clinical trial information: NCT05089734 . Median OS, mo (95% CI) HR (95% CI) SG Doc Nonresponsive (SD/PD) to last IO n = 19211.8 (9.6–12.8)0.83 (0.66–1.04) n = 1918.3 (6.9–10.2) Responsive (CR/PR) to last IO n = 1069.7 (8.4–14.3)1.05 (0.78–1.43) n = 11310.8 (9.2–12.8) Squamous n = 8410.3 (8.1–13.2)0.89 (0.63–1.25) n = 809.2 (6.9–11.0) Nonsquamous n = 21511.6 (9.4–12.9)0.89 (0.72–1.11) n = 2249.9 (7.9–11.2) With prior therapy for AGA n = 1912.9 (7.2–23.9)0.63 (0.31–1.29) n = 257.0 (5.2–11.6) TEAE, % (safety population)Any gradeGrade ≥3Serious TEAEsLeading to dose reductionLeading to discontinuationTRAEs leading to discontinuationLeading to deathTRAEs leading to death n = 296 99.768.647.629.710.17.43.41.4 n = 288 98.376.044.439.216.714.24.21.0

TPS8666 Background: Oncogenic ALK gene fusions are detected in ~5% of advanced non-small cell lung cancer (NSCLC) cases. Among these patients, the incidence of brain metastases at diagnosis is ~40%. Prior generations of ALK tyrosine kinase inhibitors (TKIs) present limitations that may influence efficacy and tolerability, such as inadequate control of brain metastases, treatment-emergent drug-resistant ALK mutations, or off-target adverse events, particularly neurological events associated with inhibition of the structurally related TRK kinases. Neladalkib is a potent, brain-penetrant, ALK-selective TKI with preclinical activity against diverse ALK fusions and resistance mutations (Lin et al., Cancer Discovery 2024). In the Phase 1/2 ALKOVE-1 study, neladalkib showed encouraging preliminary efficacy in patients with heavily pretreated ALK+ NSCLC, including in those with ALK single or compound resistance mutations and brain metastases (Drilon et al., ESMO 2024). It also exhibited a favorable safety profile consistent with its ALK-selective, TRK-sparing design. The Phase 3 ALKAZAR study aims to demonstrate the superiority of neladalkib over a current standard of care, alectinib, in TKI-naïve patients with advanced ALK+ NSCLC. Methods: ALKAZAR (NCT06765109) is a global, Phase 3, randomized, controlled, open-label study in adult patients with locally advanced or metastatic NSCLC harboring an ALK rearrangement per local testing of tissue or blood. Prior systemic anticancer treatment for metastatic disease is not allowed. Patients who received prior alectinib in the adjuvant setting are not eligible. Patients are required to have measurable disease by RECIST. Patients with untreated central nervous system (CNS) disease without progressive neurological symptoms or increasing corticosteroid doses are eligible. Patients with non-ALK oncogenic driver alterations are excluded. Approximately 450 patients will be randomized in a 1:1 ratio to receive either oral neladalkib (150 mg once daily) or oral alectinib (600 mg twice daily), stratified by brain metastases, ethnic origin (Asian vs. non-Asian), and Eastern Cooperative Oncology Group (ECOG) performance status (PS) score (0 vs.1 vs. 2). The primary endpoint is progression-free survival by blinded independent central review. Secondary endpoints include intracranial activity, objective response rate, duration of response, overall survival, safety and tolerability, and patient-reported outcomes. Additional analyses will be conducted to investigate candidate biomarkers and molecular mechanisms of response and resistance to neladalkib and alectinib. The study is open to accrual. Clinical trial information: NCT06765109 .

Background Patients with locally advanced non-small-cell lung cancer (NSCLC) who undergo concurrent chemotherapy and radiotherapy often experience synergistic toxicity, and local regional control rates remain poor. We assessed the activity and safety outcomes of primary tumour stereotactic body radiotherapy (SBRT) followed by conventional chemoradiotherapy to the lymph nodes and consolidation immunotherapy in patients with unresectable locally advanced NSCLC. Methods In this multicentre, single-arm, phase 2 trial, patients aged 18 years and older were enrolled at eight regional cancer centres in North Carolina and South Carolina, USA. Patients were eligible if they had stage II-III, unresectable, locally advanced NSCLC (any histology), with peripheral or central primary tumours that were 7 cm or smaller, excluding central tumours within 2 cm of involved nodal disease, and an Eastern Cooperative Oncology Group performance status of 0-2. Patients who had previously received systemic therapy or radiotherapy were excluded. Participants received SBRT to the primary tumour (50-54 Gy in three to five fractions) followed by standard radiotherapy (planned up to 60 Gy in 30 2 Gy fractions) to the involved lymph nodes with concurrent platinum doublet chemotherapy (either paclitaxel 50 mg/m2 intravenously plus carboplatin area under the curve mg/mL per min every 7 days for a total of six 1-week cycles or etoposide 50 mg/m2 intravenously on days 1-5 and days 29-33 plus cisplatin 50 mg/m2 intravenously on days 1, 8, 29, and 36 for two cycles of 4 weeks). An amendment to the protocol (Dec 11, 2017) permitted the administration of consolidation durvalumab at the discretion of the treating investigator. An additional protocol amendment on Jan 13, 2021, directed patients without disease progression after chemoradiotherapy to receive consolidation durvalumab (10 mg/kg intravenously on day 1 and day 15 of a 4-week cycle for up to 12 cycles or 1500 mg intravenously on day 1 of a 4-week cycle for up to 12 cycles). The primary endpoint was 1-year progression-free survival (per Response Evaluation Criteria in Solid Tumours version 1.1), assessed in all participants who received at least one fraction of SBRT and had radiological follow-up data up to 1 year. A 1-year progression-free survival rate of greater than 60% was required to reject the null hypothesis and show significant improvement in 1-year progression-free survival. One-sided exact binomial tests were used to compare the primary endpoint versus the historical control 1-year progression-free survival rate used to determine the sample size. Safety was assessed in all patients who received at least one fraction of SBRT. This study is registered with ClinicalTrials.gov, NCT03141359, and is closed to accrual. Findings Between May 11, 2017, and June 27, 2022, 61 patients were enrolled and received at least one dose of fractionated SBRT, of whom 59 were evaluable for the primary endpoint. Median age was 67 years (IQR 61-72), 28 (46%) of 61 were female, 33 (54%) were male, 51 (84%) were White, seven (11%) were Black, and three (5%) were of other or unknown race. Of the 61 patients enrolled, 47 received at least one dose of consolidation durvalumab. As of data cutoff (July 12, 2023), median follow-up was 295 months (IQR 149-471). 1-year progression-free survival was 627% (90% CI 512-732; one-sided p=039, compared with the historical control rate), with 37 of 59 evaluable participants progression free and alive 1 year after enrolment (n=14 progressed, n=8 died). The most common grade 3-4 treatment-related adverse events were decreased neutrophil count (nine [15%] of 61 patients), decreased white blood cell count (five [8%]), and anaemia (four [7%]). Treatment-related serious adverse events occurred in 11 (18%) of 61 patients, which included lung infection (three [5%]), pneumonitis (two [3%]), decreased neutrophil count (two [3%]), febrile neutropenia (two [3%]), and dyspnoea, hypoxia, respiratory failure, sinus tachycardia, bronchial infection, and acute kidney injury (each in one [2%] patient). Treatment-related deaths occurred in four (7%) of 61 patients (one each of respiratory failure, respiratory failure and dyspnoea, lung infection, and pneumonitis). Copyright (c) 2024 Elsevier Ltd. All rights reserved, including those for text and data mining, AI training, and similar technologies.

Background: These are the efficacy and toxicity outcomes of a prospective phase II trial of primary tumor stereotactic body radiation (SBRT) followed by conventional chemoradiation to the lymph nodes and consolidation immunotherapy in patients with unresectable locally advanced non-small cell lung cancer (LA NSCLC). Methods: Eligible patients included stages II-III LA NSCLC with peripheral primary tumors ≤7 cm or centrally-based tumors with ≥2 cm separation from involved nodal disease. Patients received SBRT to the primary tumor (50-54 Gy in 3-5 fractions) followed by standard radiation (60 Gy in 30 fractions) to the involved lymph nodes with concurrent platinum-doublet chemotherapy. Trial amendment allowed patients without disease progression after chemoradiation to receive consolidation durvalumab. The primary endpoint was 1-year progression-free survival (PFS). Frequencies and proportions were used for reporting this primary endpoint, adverse events, and patterns of failure. Time to event endpoints, including PFS and overall survival (OS), were estimated using Kaplan Meier (KM) methods. Findings: 61 patients across 8 centers were enrolled, including 59 evaluable for the primary objective, with a median follow-up of 48.1 months. Overall grade 3 or higher toxicity related to SBRT and/or mediastinal radiation was 13·1%, with three patients (5%) developing grade 3 pneumonitis. KM-estimated PFS at 1-year for all patients was 62.8%, median PFS was 25·3 months (95% CI: 11·5, 54·1), and median OS was 47·1 months. Of the 61 patients enrolled, 47 received at least one dose of consolidation durvalumab. The KM-estimated 1-year PFS for patients who received durvalumab was 69·6%. Interpretation: SBRT to the primary tumor followed by conventional chemoradiation to the involved lymph nodes and consolidation immunotherapy was well tolerated and showed improved 1-year PFS compared to prior conventional chemoradiation trials for inoperable LA NSCLC. These findings serve as the basis for the randomized phase III study NRG Oncology LU008 (NCT05624996).Trial Registration: The trial is registered with ClinicalTrials.gov, NCT03141359.Funding: This research was supported by AstraZeneca and Atrium Health Levine Cancer.Declaration of Interest: The authors have no potential competing interests to report.Ethical Approval: This was an open-label, single-arm, phase II study approved by our Institutional Review Board and monitored by our institutional data and safety monitoring committee. All participants provided written informed consent to participate. The trial was conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonization Guidelines for Good Clinical Practice at eight different centers within North and South Carolina all within the Levine Cancer Institute Atrium Health network. The trial was conducted in accordance with the Declaration of Helsinki and the International Conference on Harmonization Guidelines for Good Clinical Practice and approved by the IRB of the Levine Cancer Institute Atrium Health network (IRB approval number Pro00021247).

Limited treatment options exist for patients with advanced non-small cell lung cancer (aNSCLC) progressing on platinum-based chemotherapy (chemo) and immunotherapy (IO). Moreover, real-world (RW) data on the use of and outcomes with taxanes and other recommended chemo treatments in this setting during the current IO era are limited. Existing RW evidence predominantly focuses on specific taxane treatments and excludes patients with targeted mutations. Considering these evidence gaps, we evaluated RW treatment patterns and clinical outcomes in patients with aNSCLC who received chemo after prior platinum chemo-IO treatment in the US.

e24035 Background: The use of performance status (PS) assessments in patients with cancer is a common practice to determine their suitability for treatment, clinical trial enrollment, and prognosis. The Karnofsky Performance Scale (KPS) and Eastern Cooperative Oncology Group Performance Status (ECOG PS) score are widely used clinical instruments for this purpose. However, these tools are subjective and unidimensional, with potential for bias, and were validated in younger patients. KPS has demonstrated greater specificity than ECOG in evaluating PS. Frailty, a dynamic medical syndrome characterized by diminished strength, endurance, and reduced physiological function, is recognized as a predictor of vulnerability to adverse outcomes, especially in older adults with cancer. The Fried Frailty Phenotype (FP) is a widely validated tool that uses both objective and subjective measures to identify frailty based on presence of 3 or more criteria: unintentional weight loss, self-report of exhaustion (fatigue), weakness (measured by grip strength), slow walking speed, and low physical activity. Our study compares physician-rated KPS with FP (fit, prefrail, frail) and looks at correlation of both tools in older adults with cancer. Methods: Data from older adults with solid tumor malignancies referred to the geriatric oncology clinic for geriatric assessment (GA) from January 2015–August 2019 were abstracted. Physician-rated KPS (0-100) were categorized into 3 groups: normal activity, high functioning (80–100); intermediate, capable of self-care but unable to do active work (70); and poor PS, requires considerable assistance (<60). These were compared to FP which classified patients based on the number of frailty criteria present: fit (0), prefrail (1-2), and frail (>3). Frequency data calculation and bivariate analysis were done. Results: 241 older adults with cancer completed a GA, median age of 80 years, 52% female. 57% were frail, 37% prefrail, and 6% fit. 90% of patients with KPS 80-100, had prefrail and frail phenotypes. Patients with KPS 70 had 24% prefrail and 76% frail phenotypes and those with KPS < 60 had 10% prefrail and 90% frail phenotypes. Conclusions: Majority of older patients with prefrail and frail phenotypes were assessed as high functioning (KPS 80-100). KPS is an inadequate substitute for FP and should not be used alone in assessing functional status of older adults with cancer.

Oncogenic ROS1 gene fusions are implicated in the pathogenesis of various adult and pediatric cancers, including up to 3% of non-small cell lung cancers (NSCLC), where up to 40% of patients present with central nervous system (CNS) metastases. Tyrosine kinase inhibitors (TKIs) approved by the FDA and EMA for ROS1-positive NSCLC (crizotinib and entrectinib) are limited by acquired resistance, frequently mediated by secondary ROS1 kinase domain mutations. In addition, dual TRK/ROS1 kinase inhibitors such as entrectinib are associated with neurologic adverse events.

Oncogenic ROS1 gene rearrangements are implicated in the pathogenesis of various adult and pediatric cancers, including up to 3% of non-small cell lung cancers (NSCLC), where up to 40% of patients present with central nervous system (CNS) metastases. Tyrosine kinase inhibitors (TKIs) approved by the FDA and EMA for ROS1-positive NSCLC (crizotinib and entrectinib) are limited by acquired resistance, frequently mediated by secondary ROS1 kinase domain mutations. In addition, dual TRK/ROS1 kinase inhibitors, including entrectinib, are associated with neurologic adverse events. NVL-520 is a novel, brain-penetrant ROS1-selective kinase inhibitor that exhibits preclinical activity against a diverse array of ROS1 rearrangements and mutations, including G2032R, while sparing inhibition of TRKB. The ARROS-1 study evaluates the safety and activity of NVL-520 in patients with solid tumors harboring ROS1 fusions, including those with resistance mutations and CNS metastases. ARROS-1 (NCT05118789) consists of a phase 1 dose escalation followed by phase 2 expansion in cohorts defined by tumor type and prior therapies that are designed to support potential registration. Phase 1 includes adult patients with any solid tumor type harboring a ROS1 gene fusion (by local testing), with evaluable disease, who have received ≥ 1 ROS1 TKI. Prior platinum-based chemotherapies and/or immunotherapies, as well as stable CNS disease, are allowed. Patients will receive NVL-520 by daily oral administration. Primary phase 1 objectives are to determine the NVL-520 recommended phase 2 dose, and, if applicable, maximum tolerated dose. Additional objectives include evaluation of safety/tolerability, preliminary activity, and characterization of the pharmacokinetic and pharmacodynamic profiles of NVL-520. Longitudinal analysis of circulating tumor DNA will be performed, including ROS1 mutation profiling and other relevant biomarkers. The phase 1 portion of the study is ongoing. NCT05118789 (November 12, 2021). Nuvalent, Inc. Nuvalent, Inc.

Background Despite the preclinical promise of CD40 and 4-1BB as immuno-oncologic targets, clinical efforts evaluating these agonists as monotherapy have had limited success due to minimal efficacy and/or severe toxicity. DuoBody-CD40×4-1BB (GEN1042) is a first-in-class, bispecific, agonistic antibody that combines targeting and conditional activation of CD40 and 4-1BB on immune cells, resulting in enhanced priming and (re-)activation of tumor-specific immunity. Furthermore, preclinical data suggest that combination with anti–PD-1 can enhance antitumor activity. We present preliminary data from the ongoing, first-in-human, open-label, phase 1/2 trial of DuoBody-CD40×4-1BB in advanced solid tumors ( NCT04083599 ). Methods During dose escalation, patients with metastatic/unresectable non-CNS solid tumors who had exhausted standard therapies received flat-dose DuoBody-CD40×4-1BB (0.1–400 mg) intravenously every 3 weeks until disease progression or unacceptable toxicity. Primary endpoint was dose-limiting toxicity (DLT). Secondary endpoints included adverse events (AEs), pharmacokinetic parameters, and preliminary antitumor activity (RECIST v1.1). Pharmacodynamic biomarkers were assessed as exploratory endpoints. Results As of June 11, 2021, 50 patients were enrolled (median age, 57 years). The most common cancer types were colorectal (22%), melanoma (20%), and non–small-cell lung cancer (8%). Patients received a median (range) of 2.5 (1–21) treatment cycles; Cmax was observed shortly after end of infusion. Treatment-related AEs occurring in ≥10% of patients (all grades; grade ≥3) were fatigue (22%; 0%), pyrexia (16%; 0%), nausea (10%; 0%), and transaminase elevation (10%; 6%). Maximum tolerated dose was not reached. One DLT of elevated transaminases (grade 4) was observed at the 200-mg dose that resolved upon corticosteroid administration. No drug-related grade ≥3 thrombocytopenia events were reported. Disease control, defined as best overall response of complete/partial response and stable disease, was achieved in 51% of patients (25/49), including 2 confirmed partial responses per RECIST v1.1 in melanoma and neuroendocrine lung cancer. Modulation of pharmacodynamic endpoints was observed across dose levels, with more pronounced effects near the 100-mg dose. Increases in peripheral IFN-y, TARC (monocyte/DC chemokine), and proliferating CD8+ total and effector memory T cells were observed during cycle 1. Using physiologically based pharmacokinetic/pharmacodynamic modeling and available safety, efficacy, and pharmacodynamic data, 100 mg every 3 weeks was identified as the expansion dose for further evaluation. Conclusions DuoBody-CD40×4-1BB demonstrated biologic and early antitumor activity with a favorable safety profile in patients with advanced solid tumors. Expansion cohorts, including combination therapy with PD-1 inhibitors, are currently enrolling. Acknowledgements This trial was funded by Genmab A/S and BioNTech SE. Trial Registration NCT04083599 Ethics Approval This trial is undertaken following full approval of the final protocol, amendments, informed consent form, applicable recruiting materials, and subject compensation programs by the Independent Ethics Committee/Institutional Review Board.

e21192 Background: Landmark trials have shown increased survival in pts who receive IO for NSCLC as compared to chemotherapy (chemo). Median overall survival (mOS) ranged from 17-26 months (mo); however, mOS in several published “real-world” retrospective studies are lower, ranging from 8-12 mo, with about 4-5 months on IO treatment. We sought to define mOS of pts with mNSCLC who received IO as monotherapy or in combination with chemo as first line therapy at Levine Cancer Institute. Methods: We retrospectively reviewed 315 adult pts with mNSCLC without driver mutations diagnosed between 2016 and 2019. The Kaplan-Meier method was used to estimate and compare OS between IO and IO + chemo. Univariate and multivariate Cox models were used to evaluate risk factors (RF) for OS. RFs considered included age, sex, race, smoking status, histology, first-line treatment type, and metastatic (mets) sites. Results: Baseline pt characteristics were: 40% female, 77% white, 20% Black, 34% current smokers and 60% former smokers. Median age was 69 years (45-88) in pts receiving IO alone and 63 years (28-84) in pts receiving IO + chemo. Tumor characteristics were: 76% adenocarcinoma and 17% squamous cell carcinoma. PD-L1 TPS distribution was: 39% for 0%, 22% for 1-49%, and 39% for ≥50%. Distribution of mets was 10% adrenal, 40% bone, 30% brain, 14% liver, 31% lung. mOS for pts receiving IO and IO + chemo as first line therapy was 17 and 14.8 mos, respectively (P = .209). Median duration of IO received was 4.25 months (0 to 43.6). mOS as stratified by PD-L1 TPS was 14.5 mos for PD-L1 0%, 13.3 mos for PD-L1 1-49%, and 19.5 mos for PD-L1 ≥50% (P = .163). OS was significantly different between IO and IO + chemo after adjusting for age. No OS differences were seen between white and Black or between all pts vs pts with brain mets (brain-specific interventions not reviewed). The table summarizes significant findings only (P < 0.05). Conclusions: Pts with mNSCLC treated first-line with IO either alone or with chemo at Levine Cancer Institute lived longer than those in similar published “real-world” cohorts. Median OS was highest in patients with PD-L1 TPS ≥50%, although not statistically significant. While not unusual to identify worse outcomes in those with bone and liver mets, interestingly brain metastasis was not associated with worse survival. In this cohort, when adjusted for age, IO alone trends toward improved survival. Although there was no OS difference based on race, further investigation will seek to uncover any other disparities contributing to outcomes, such as insurance status and zip code mapping. To our knowledge, this provides the largest analysis of this patient population outside of a clinical trial.[Table: see text]

e21047 Background: The care of pts with locally-advanced NSCLC has continued to evolve. Dose escalation with conventional radiation and concurrent chemotherapy has failed to improve outcomes and is associated with low primary tumor control rates and high toxicity rates. We initiated a phase II study to evaluate full dose SBRT to the primary tumor followed by conventional chemoradiation to the involved lymph nodes followed by adjuvant immunotherapy in patients (pts) with unresectable locally-advanced NSCLC. Methods: Eligible pts included peripheral primary tumors ≤ 7cm or centrally based tumors that had at least 2 cm separation from involved nodal disease. Pts received SBRT to the primary tumor (50-54 Gy in 3-5 fractions) followed by standard radiation to 60 Gy in 30 fractions with concurrent chemotherapy (physician choice of carboplatin/paclitaxel or cisplatin/etoposide). Pts without disease progression after chemoradiation then received adjuvant durvalumab (PACIFIC trial). Planned analysis of early toxicity was performed given this is the first prospective trial to replace conventional fractionation and deliver full dose SBRT to the primary tumor in the locally advanced setting. Results: From May 2017 to January 2020, 35pts were enrolled. Median follow up is 7.9 months (range 0-27 months). Toxicity related to either SBRT or mediastinal radiation was lower than previous published prospective trials with a grade 2 radiation pneumonitis incidence of only 17%. There was no ≥grade 3 pneumonitis. Grade 3 esophagitis was observed in 1 pt (3%) with grade 2 esophagitis in 37%. No grade ≥3 toxicity has been attributed to SBRT with 26% of pts experiencing a grade 2 toxicity from SBRT. Overall incidence of grade ≥3 pulmonary toxicity attributed to any therapy was 9%. One pt died of neutropenic sepsis due to legionella while on therapy attributed to chemotherapy. No major cardiac events were reported to date. Conclusions: Full dose SBRT to the primary tumor followed by standard chemoradiation to the involved lymph nodes appears to have a favorable toxicity profile when compared with conventional dose escalation and to previously published experiences with SBRT boost following chemoradiation in the treatment of locally advanced NSCLC. Our trial continues to enroll with a target of 56 pts. Clinical trial information: NCT03141359 .

PURPOSE The Targeted Agent and Profiling Utilization Registry (TAPUR) Study is a phase II pragmatic basket trial evaluating antitumor activity of commercially available targeted agents in patients with advanced cancer with genomic alterations known to be drug targets. Results in a cohort of patients with non–small-cell lung cancer (NSCLC) with CDKN2A alterations treated with palbociclib are reported. METHODS Eligible patients were ≥ 18 years old with advanced NSCLC, no remaining standard treatment options, measurable disease, Eastern Cooperative Oncology Group performance status of 0 to 2, and adequate organ function. Patients with NSCLC with CDKN2A alterations and no Rb mutations received palbociclib 125 mg orally once daily for 21 days, followed by 7 days off. Simon’s two-stage design was used with a primary study end point of objective response or stable disease (SD) of at least 16 weeks in duration. Secondary end points are progression-free survival (PFS), overall survival (OS), and safety. RESULTS Twenty-nine patients were enrolled from January 2017 to June 2018; two patients were not evaluable for response but were included in safety analyses. One patient with partial response and six patients with SD were observed, for a disease control rate of 31% (90% CI, 19% to 40%). Median PFS was 8.1 weeks (95% CI, 7.1 to 16.0 weeks), and median OS was 21.6 weeks (95% CI, 14.1 to 41.1 weeks). Eleven patients had at least 1 grade 3 or 4 adverse event (AE) or serious AE (SAE) possibly related to palbociclib (most common, cytopenias). Other AEs or SAEs possibly related to the treatment included anorexia, fatigue, febrile neutropenia, hypophosphatemia, sepsis, and vomiting. CONCLUSION Palbociclib monotherapy demonstrated evidence of modest antitumor activity in heavily pretreated patients with NSCLC with CDKN2A alterations. Additional investigation is necessary to confirm efficacy and utility of palbociclib in this population.

The median number of medications taken by adults aged 65 and older is four, but may be higher in older adults with cancer. A high number of prescribed medications increases risk for adverse drug reactions (ADRs), drug-drug interactions, drug-disease interactions, and overall healthcare utilization, emphasizing the need for frequent review of medications. There are many tools available to help the health care team assess medication appropriateness; however, none of the currently available tools have been validated in the geriatric oncology population. Older adults with cancer are at increased risk for ADRs and potentially inappropriate medications (PIMs) given the common need for multiple medications to manage cancer and cancer-related symptoms. Frequently used PIM identification tools, such as the American Geriatrics Society's (AGS) Beers criteria, often identify medications as “potentially inappropriate”, although many of these medications are considered necessary to provide adequate supportive care in older patients with cancer. There are currently no specific guidelines to help direct application of available tools. This review summarizes literature available on the use of PIM identification tools in geriatric oncology and highlights a theoretical case and proposed medication management strategy, which combines the use of objective review with Beer's criteria and clinical judgement with the Medication Appropriateness Index (MAI). This two-pronged approach can serve to identify PIMs while recognizing factors unique to the geriatric oncology population.

Abstract BACKGROUND The median age at diagnosis for high grade glioma is 64 years. With peak incidence 75-84, malignant glial tumors are frequently a disease of the elderly. Common assessment measures fail to accurately gauge geriatric cancer patient fitness. Comprehensive Geriatric Assessment (CGA) is recommended in patients older than 65 to gauge risk of toxicity and tolerance of therapeutic intervention. We reviewed data for older patients with high grade glioma (HGG) and thoracic malignancy (TM) who underwent CGA via Senior Oncology Clinic (SOC) at Levine Cancer Institute. METHODS From 2015 to 2019 104 thoracic malignancy patients and 19 high grade glioma patients completed CGA via SOC before treatment or a required change in therapy. Data was incorporated into the LCI Senior Oncology Database by the REDCap secure web application, allowing for both quantitative and qualitative data analysis. RESULTS The median age was 77 in the HGG cohort compared to 80 years with TM. The physician rated Karnofsky Performance Status (KPS) for HGG and TM were similar (76% v 79%) as were the percentages of patients that were frail or prefrail (90% v 87%). Montreal Cognitive Assessment scores were lower in HGG (20 v 23). Considerably more HGG had falls in the 6 months before their assessment (58% v 30%) and gait speed was slower (0.76 m/s v 0.85 m/s). CONCLUSIONS Older patients with high grade gliomas compared to similar thoracic malignancies had more neurocognitive impairment, falls in the preceding 6 months, and slower gait speed. Physician rated KPS and frailty were similar in both groups. The results illustrate the limitations of physician-rated performance measures and highlight the importance of CGA in older brain tumor patients.

122 Background: The incidence of cancer in patients older than 65 is nearly tenfold higher than in their younger counterparts. Comprehensive geriatric assessment (CGA) is recommended for cancer patients > 65 years, as it can more reliably assess underlying function and predict tolerance to anticancer therapy. We reviewed data for patients with lung cancer and hematologic malignancies who completed comprehensive geriatric assessment by the Senior Oncology Section within the Levine Cancer Institute. Methods: From 2015 to 2019 Levine Cancer Institute (LCI) providers performed 96 CGAs in lung cancer patients and 58 in patients with hematologic malignancy, many of the latter being evaluated for bone marrow transplantation. Data was incorporated into an LCI Senior Oncology Clinic Database using the REDCap secure web application, allowing both quantitative and qualitative data analysis. Results: Median ages were 80 in lung cancer and 67 in hematologic malignancy. The lung cancer patients had a slower gait than patients with hematologic malignancy (0.8 m/s versus 1.3 m/s). Lung cancer patients also had a longer median timed up and go (TUG) test of 13 seconds, versus 8 seconds in hematologic malignancy. Considerably more lung cancer patients had experienced a fall within the preceding six months (32 (33%) versus 9 (16%)). The median Cumulative Illness Rating Scale-Geriatric (CIRS-G) total score was significantly higher in lung than in hematologic malignancy (14 versus 8), indicating a higher degree of comorbid illness. Cognitive functioning was comparable between the two groups, with median Montreal Cognitive Assessment (MoCA) scores of 25 in lung and 26 in hematologic malignancy. Conclusions: Lung cancer patients undergoing CGA had more comorbid illnesses, slower gait speed and timed up and go, and more falls in the preceding 6 months than hematologic malignancy patients. Overall cognitive functioning was not significantly different between the two groups. These findings highlight the importance of comprehensive geriatric assessment in elderly lung cancer patients. [Table: see text]