Significant Improvement In OS Research Articles

Abstract IA21: Biomarker-informed studies in peripheral T-cell lymphoma

Abstract Peripheral T-cell lymphomas (PTCL) are a heterogeneous group of non-Hodgkin's lymphomas (NHL) with 29 distinct subtypes (counting provisional entities) in the latest WHO classification (1). Historically, therapeutic approaches for PTCL were derived from aggressive B-cell lymphomas. More recent therapies have been studied specifically in PTCL with four drugs approved by the FDA in the last decade, including pralatrexate, romidepsin, brentuximab vedotin (ALCL only), and belinostat (2-5). The most frequent approach to studying new agents has been empiric with some continued success in identifying additional tools, with “all-comer” overall response rates between 25-30% and only moderate durability (median PFS 2.5-4 months). The one standardly used exception is the CD30 targeted antibody drug conjugate brentuximab vedotin. When the CD30 target is strongly and consistently expressed as in anaplastic large-cell lymphoma, brentuximab vedotin is remarkably active with an overall response rate of 86% (57% CR) and a median PFS >12 months (4). Brentuximab vedotin has activity in other variably CD30-expressing PTCL including AITL, PTCL-NOS, and MF, although the consistency, depth, and duration of responses are less than those seen in ALCL (6-7). Whether those differences are explained primarily by the density and intensity of target as opposed to the underlying biology of those diseases is unclear. Nonetheless, when BV was added to upfront chemotherapy for patients with untreated PTCL, and enriched for those with CD30 expression, significant improvements in PFS and OS were seen with the greatest benefit for those with ALCL (8). In an attempt to expedite our understanding and application of new therapies in T-cell lymphoma, we expanded and formalized a clinical research partnership in part supported by an LLS SCOR grant (Translational Discovery in Peripheral T-cell lymphoma; PI David Weinstock) to prospectively incorporate correlative science plans and institute standards of sample collection into new clinical trials of targeted agents. Several of our initial trials have shown efficacy at times in subtype-specific ways. The SYK/JAK inhibitor cerdulatinib (NCT01994382) showed particular activity in AITL and intriguing but transient activity in several subjects with strong syk-expressing g/d TCLs but an absence of activity in those with PTCL-NOS (9). For the Pi3K d/g inhibitor duvelisib as part of combination therapy (NCT02783625), the responses and complete responses were consistent across subtypes (10). In that trial over 80% of subjects had samples collected, and RNAseq, whole-exome sequencing, and multicolor immunofluorescence are being conducted. For the trial of ruxolitinib, we set out to both test a prespecified hypothesis and collect tissues pretreatment, on treatment, and at relapse to assess additional predicators of response and understand mechanisms of resistance. In this study (NCT02974647, PI Alison Moskowitz). We divided patients into cohorts based on presence of JAK/STAT mutation (Cohort 1), absence of mutation but presence of phosphorylated (p)STAT3 or pSTAT5 by IHC/phosphoflow (Cohort 2), or neither (Cohort 3). As hypothesized, absence of either pathway activation or mutation was associated with low rates of response, and preliminary assessment of pretreatment biopsies by multicolor immunofluorescence identified pS6 as a predictive biomarker to inform subsequent studies of ruxolitinib in PTCL (11). These early attempts have demonstrated a proof of principle that biomarker-driven hypotheses can be embedded into prospective clinical trials of PTCL and adequate sample collection is feasible. These samples allow us to best match therapies to patients and, critically, by obtaining samples on treatment and at progression, provide the best opportunity to understand mechanisms of resistance to facilitate the design of combination therapies.

ALL-232: Genetic Variants of Tumor Necrosis Factor α and Interleukin-10 in Childhood and Adult Acute Lymphoblastic Leukemia

Context Interleukin-(IL)10 and tumor necrosis factor (TNF) a have a significant role in malignancies. Genes encoding these cytokines are linked with different levels of gene transcription. Objective Analyzing IL-10 and TNFα gene polymorphisms and their contribution to ALL prognosis and survival. Design This prospective observational study was conducted from June 2017 until Oct 2019. Setting Oncology Center Mansoura University, Egypt. Patients or other participants We genotyped 64 children and 76 adult ALL patients for IL-10-1082A > G and TNFα-308G > A polymorphisms in the gene promoter region. We used polymerase chain reaction (restriction fragment length polymorphism method) for the molecular analysis. Results Pediatric ALL patients showed TNFα A allele and IL-10 A allele, which were associated with older age (p = 0.04, 0.03), extramedullary disease (p = 0.04, 0.001), and carried Philadelphia chromosome (p = 0.02, 0.001), compared to the G allele, respectively. IL-10-1082AA and TNF 308AA genotypes carried on the Ph-positive chromosome were associated with a longer time to CR and a higher rate of relapse than other genotypes. The IL-10 (GG) genotype was associated with significant improvement of OS compared to IL-10 (GA) and (AA) genotypes (p = 0.026). The adult ALL patients carrying the A allele of TNFα had a higher rate extramedullary disease (p = 0.009) and a higher rate of relapse (p = 0.003). Also, we found increased frequency of the IL-10-A allele with advanced age (p = 0.03), lower Hb level (p = 0.04), increased extramedullary disease (p = 0.001), and Ph chromosome positivity (p = 0.001), which resulted in longer time to CR (p = 0.003) and high relapse rate (p = 0.002). IL-10 (AA) and TNFα (AA) genotype patients were associated with extramedullary disease, carried the Ph-positive chromosomal abnormality, and had a higher rate of relapse than other genotypes among adult ALL patients. Patients with IL-10 (GG) and TNFα (GG) genotypes did not show significant improvement of OS and RFS by Kaplan-Meier curves (p > 0.05) compared to other genotypes. Conclusion IL-10 (AA) and TNFα (AA) were associated with poor prognostic factors in childhood and adulthood ALL. This might modulate the risk, overall survival, and relapse-free survival among ALL patients.

293P Impact of tucatinib on progression free survival in patients with HER2+ metastatic breast cancer and stable or active brain metastases

Up to 50% of HER2+ metastatic breast cancer (MBC) pts will develop brain metastases (BM) for which effective treatments are needed. In the HER2CLIMB (NCT02614794) double-blind trial, tucatinib (TUC) added to trastuzumab (T) and capecitabine (C) resulted in statistically significant improvements in PFS and OS in HER2+ MBC pts with and without BM (Murthy, NEJM 2019). Risk of disease progression or death in BM pts was 52% lower in the TUC arm vs. the control arm (P<0.001). We present exploratory analyses of PFS by type of BM in HER2CLIMB. HER2CLIMB pts were randomized 2:1 to receive TUC or placebo combined with T and C. All pts had baseline brain MRI. BM were classified as untreated, treated stable, or treated and progressing. PFS per investigator and OS were analyzed by treatment arm in stable BM pts (treated stable) and active BM pts (untreated + treated progressing), using standard RECIST 1.1 assessing disease in both body and brain. At baseline, 291 pts (48%) had BM: 198 (48%) in the TUC arm and 93 (46%) in the control arm. In pts with stable BM (n=117), risk of disease progression or death was reduced by 44% in the TUC arm (HR: 0.56; 95% CI: 0.33, 0.96; P=0.03); median (95% CI) PFS was 7.5 mo (5.4, 9.6) in the TUC arm vs. 5.0 mo (2.0, 5.6) in the control arm. In pts with active BM (n=174), risk of disease progression or death was reduced by 62% in the TUC arm (HR: 0.38; 95% CI: 025, 0.58; P<0.00001); median PFS was 7.6 mo (5.7, 8.5) in the TUC arm vs. 4.1 mo (3.1, 4.3) in the control arm. In pts with treated progressing BM (n=108), risk of disease progression or death was reduced by 64% in the TUC arm (HR: 0.36; 95% CI: 0.21, 0.63; P=0.0002); median PFS was 7.6 mo (5.7, 9.6) in the TUC arm vs. 4.1 mo (3.1, 4.3) in the control arm. In pts with untreated BM (n=66), risk of disease progression or death was reduced by 53% in the TUC arm (HR: 0.47; 95% CI: 0.24, 0.92; P=0.02); median PFS was 6.9 mo (5.5, 9.6) in the TUC arm vs. 3.6 mo (1.5, 7.5) in the control arm. Addition of TUC to T and C significantly improved PFS regardless of BM type, indicating delay of progression not only in the body but also in the brain. Patients with active BM (typically excluded from HER2+ MBC trials) had substantially longer PFS with TUC treatment.

Steroid-refractory acute graft-versus-host disease graded III-IV in pediatric patients. A mono-institutional experience with a long-term follow-up.

aGvHD remains a major obstacle to successful HSCT. We report our experience on steroid-refractory aGvHD III and IV from 1989 to 2017. Ninety patients with aGvHD III or IV were stratified according to the HSCT year: 1989-1998, 1999-2007, and 2008-2017 and to aGvHD extension (GvHD III vs IV) and finally the probability of OS, RI, and TRM was calculated accordingly. aGvHD III patients had a substantial improvement over time: day 100 OS raised from 64% (95% CI 39-89) in the first cohort to 100% in the latest (P=.022), and it was mainly due to a reduction of TRM (it was 28% [95% CI 12-65] in the first cohort to 0% in the latest (P=.01). The aGvHD IV patients did not present a significant improvement. Day 100 OS was 42% (95% CI 16-68) in the first group and 54% (95% CI 25-83) in the year 2008-2017 (P=NS), and the day-100 TRM was very similar (it was 57% [95% CI 36-90] in the first cohort and 45% [95% CI 23-89] in the latest (P=NS). We report significant improvements in OS and TRM in patients diagnosed with grade III aGvHD. Patients with the most severe aGvHD appear to have no or fewer benefits on long-term outcomes.

Abstract CT220: IMpower133: Updated OS and exploratory analyses of first-line (1L) atezolizumab (atezo) + carboplatin (C) + etoposide (E) in extensive-stage SCLC (ES-SCLC)

Abstract Background: IMpower133 (NCT02763579), a global Phase I/III, randomized, double-blind, placebo (PBO)-controlled trial, showed that the addition of atezo (anti-PD-L1) to CE for 1L ES-SCLC led to statistically and clinically significant OS and PFS improvement vs CE alone. Here we report updated OS and exploratory analyses. Methods: Pts with untreated ES-SCLC were randomized 1:1 to receive four 21-day cycles of E (100 mg/m2 IV, days 1-3) + C (AUC 5 mg/mL/min IV, day 1) with atezo (1200 mg IV, day 1) or PBO, followed by maintenance therapy with atezo or PBO until intolerable toxicity, progression or loss of clinical benefit. PD-L1 testing was not required for enrollment. Coprimary endpoints were investigator-assessed PFS (RECIST 1.1) and OS. Interim and final OS analyses were planned for ≈240 and ≈306 events, respectively. OS was significant at the interim analysis. Updated OS, exploratory biomarkers and patterns of disease progression were analyzed. Results: 201 and 202 pts were randomized to receive atezo+CE and PBO+CE, respectively. The median follow-up was 22.9 mo and 302 deaths had occurred. Median OS for the atezo and PBO arms was 12.3 and 10.3 mo, respectively (HR, 0.76 [95% CI: 0.60, 0.95]; descriptive P = 0.0154). At the 18-mo landmark, the OS rate was 13% higher with atezo+CE than with PBO+CE (Table). Exploratory analyses showed treatment benefit with atezo+CE regardless of biomarker status. 181 (90.0%) And 194 (96.0%) pts in the atezo+CE and PBO+CE arms, respectively, had RECIST-defined disease progression. Progression at existing, new or existing and new lesions was numerically lower with atezo+CE than with PBO+CE. Common sites of new lesions included the CNS, lung, lymph node and liver, with similar incidences between arms. Conclusion: Adding atezo to CE continued to provide OS improvement for 1L ES-SCLC in an all-comer population. The updated results of IMpower133 further support this regimen for untreated ES-SCLC. Landmark OSAtezo + CE, n = 201PBO + CE, n = 20212 Mo, n (%)93 (51.9)74 (39.0)18 Mo, n (%)61 (34.0)39(21.0)Median OS in biomarker subgroupsAtezo + CEPBO + CEITT (N = 403), mo12.310.3HR (95% CI)0.76 (0.61, 0.96)aITT-BEP (n = 137), mo9.98.9HR (95% CI)0.70 (0.48, 1.02)Non-BEP (n = 266), mo14.611.2HR (95% CI)0.81 (0.61, 1.08)PD-L1 expression, 1% TC or IC&amp;lt; 1% (n = 65), mo10.28.3HR (95% CI)0.51 (0.30, 0.89)≥ 1% (n = 72), mo9.710.6HR (95% CI)0.87 (0.51, 1.49)PD-L1 expression, 5% TC or IC&amp;lt; 5% (n = 108), mo9.28.9HR (95% CI)0.77 (0.51, 1.17)≥ 5% (n = 29), mo21.69.2HR (95% CI)0.60 (0.25, 1.46)Disease progression at sites, n (%)Atezo + CEPBO + CEExisting116 (57.7)131 (64.9)New86 (42.8)99 (49.0)Existing and new42 (20.9)57 (28.2)BEP, biomarker-evaluable population; ITT, intention-to-treat population.a Stratified HR. BEP included pts evaluable by PD-L1 IHC using the VENTANA SP263 assay. Citation Format: Leora Horn, Stephen V. Liu, Aaron S. Mansfield, Tony Mok, Arnaud Scherpereel, Niels Reinmuth, Marina Chiara Garassino, Javier De Castro Carpeno, Raffaele Califano, Makoto Nishio, Francisco Orlandi, Jorge Arturo Alatorre Alexander, Ticiana Leal, Ying Cheng, Jong-Seok Lee, Sivuonthanh Lam, Mark McCleland, Yu Deng, See Phan, Martin Reck. IMpower133: Updated OS and exploratory analyses of first-line (1L) atezolizumab (atezo) + carboplatin (C) + etoposide (E) in extensive-stage SCLC (ES-SCLC) [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT220.

Abstract CT216: IMpower150 final analysis: Efficacy of atezolizumab (atezo) + bevacizumab (bev) and chemotherapy in first-line (1L) metastatic nonsquamous (nsq) non-small cell lung cancer (NSCLC) across key subgroups

Abstract Background: The Ph III IMpower150 study (NCT02366143) showed PFS and OS benefit with atezo + bev + carboplatin (carbo) + paclitaxel (pac; ABCP; Arm B) vs bev + carbo + pac (BCP; Arm C) as 1L treatment (tx) for patients (pts) with metastatic nsq NSCLC. Clinical benefit was also seen in pts with EGFR-mutant or ALK-positive (EGFR/ALK+) tumors. We report the final efficacy analyses from IMpower150, including those of the experimental tx arm evaluating atezo + carbo + pac (ACP; Arm A) vs Arm C. Methods: The randomized, open-label, Ph III IMpower150 study evaluated ACP (Arm A) or ABCP (Arm B) vs BCP (Arm C) in pts with metastatic nsq NSCLC (N = 1202). Key eligibility criteria included no prior chemotherapy, measurable disease per RECIST 1.1 and ECOG PS 0-1. Pts were stratified by sex, baseline liver metastases (mets) and PD-L1 expression. Coprimary endpoints were investigator-assessed PFS and OS in ITT wild-type (WT; no EGFR or ALK genetic alterations) pts. Secondary endpoints included PFS and OS in the ITT and PD-L1 expression subgroups. Results: With a minimum follow-up of 32.4 mo (data cutoff: Sep 13, 2019), median OS in ITT-WT pts was 19.0 mo in Arm A vs 14.7 mo in Arm C (HR, 0.84; 95% CI: 0.71, 1.00; Table). OS improvement in the TC1/2/3 or IC1/2/3-WT PD-L1 subgroup was seen in Arm A vs C; no improvement was seen in the TC0 and IC0-WT subgroup. In pts with EGFR/ALK+ tumors and pts with baseline liver mets, OS was comparable in Arms A and C; continued OS benefit in these subgroups was seen in Arm B vs C. The safety profile of each regimen was consistent with previously reported data at the second interim OS analysis (data cutoff: Jan 22, 2018). Arm A vs Arm CArm B vs Arm CaOS HR (95% CI)Median OS, moOS HR (95% CI)Median OS, moITTb (n = 402 [Arm A]; 400 [Arm B]; 400 [Arm C])0.86 (0.73, 1.01)19.0 vs 15.00.80 (0.68, 0.95)19.8 vs 15.0ITT-WTb (n = 350 [Arm A]; 359 [Arm B]; 338 [Arm C])0.84 (0.71, 1.00)19.0 vs 14.70.80 (0.67, 0.95)19.5 vs 14.7TC1/2/3 or IC1/2/3-WT (n = 185 [Arm A]; 192 [Arm B]; 165 [Arm C])0.71 (0.55, 0.91)24.4 vs 16.00.73 (0.57, 0.94)22.5 vs 16.0TC0 and IC0-WT (n = 164 [Arm A]; 167 [Arm B]; 173 [Arm C])0.96 (0.76, 1.22)14.8 vs 14.10.90 (0.71, 1.14)16.9 vs 14.1EGFR/ALK+ (n = 52 [Arm A]; 41 [Arm B]; 62 [Arm C])1.03 (0.67, 1.58)21.2 vs 17.50.77 (0.48, 1.26)25.3 vs 17.5EGFR sensitizing (n = 33 [Arm A]; 26 [Arm B]; 32 [Arm C])1.00 (0.57, 1.74)19.0 vs 18.10.60 (0.31, 1.14)29.4 vs 18.1Liver mets ITT (n = 52 [Arm A]; 52 [Arm B]; 57 [Arm C])1.01 (0.68, 1.51)7.7 vs 9.10.67 (0.45, 1.02)13.2 vs 9.1IC, tumor-infiltrating immune cells; TC, tumor cells. TC1/2/3 or IC1/2/3 = TC ≥ 1% or IC ≥ 1% PD-L1. TC0 and IC0 = TC &amp;lt; 1% and IC &amp;lt; 1% PD-L1.aAnalysis considered final at second OS interim analysis; data shown are for descriptive purposes only.bStratified analysis. Conclusions: At the final OS analysis, IMpower150 showed numerically but not statistically significant OS improvement in Arm A vs C. Final analysis data from IMpower150 continue to show OS benefit with 1L ABCP in nsq NSCLC, including in key subgroups (sensitizing EGFR mutations, liver mets). Citation Format: Mark A. Socinski, Tony S. Mok, Makoto Nishio, Robert M. Jotte, Federico Cappuzzo, Francisco Orlandi, Daniil Stroyakovskiy, Naoyuki Nogami, Delvys Rodriguez-Abreu, Denis Moro-Sibilot, Christian A. Thomas, Fabrice Barlesi, Gene Finley, Shengchun Kong, Xiaoyan Liu, Anthony Lee, Shelley Coleman, Geetha Shankar, Martin Reck. IMpower150 final analysis: Efficacy of atezolizumab (atezo) + bevacizumab (bev) and chemotherapy in first-line (1L) metastatic nonsquamous (nsq) non-small cell lung cancer (NSCLC) across key subgroups [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr CT216.

Association between immune-related adverse events and clinical outcomes to PD-1/PD-L1 blockade in small cell lung cancer

BackgroundThe development of immune-related adverse events (irAEs) has been associated with improved efficacy of immune checkpoint inhibitors in patients with urothelial cancer, melanoma, and non-small cell lung cancer. Whether this association exists in patients with small cell lung cancer (SCLC) is currently unknown. MethodsWe conducted a multicenter retrospective study to evaluate the relationship between irAEs and immunotherapy efficacy in SCLC. To account for the lead-time bias resulting from the time-dependent nature of irAEs, the development of irAEs was considered as a time-varying covariate in univariate and multivariate Cox proportional hazard models. ResultsAmong 183 patients treated with immunotherapy, 73 (39.9%) experienced at least one irAE. Forty-two (22.9%) patients had grade 1-2 irAEs, while 31 patients (16.9%) had grade 3-4 irAEs. The median time of onset to the first irAE was 24 days (IQR: 14-55). Baseline clinicopathologic features were well balanced between patients with and without irAEs. At a median follow-up of 24 months (95%CI:17.0-31.6), the median progression-free survival (mPFS) was significantly longer in the irAE group compared to the non-irAE group (3.8 versus 1.3 months, P<0.0001). The median overall survival (mOS) was also significantly longer among patients with irAEs compared to patients without irAEs (13.8 versus 2.9 months, P<0.0001). When analyzed as a time-varying covariate, the development of irAEs was associated with a significant improvement in PFS (HR:0.44 [95%CI:0.29-0.66], P<0.001) and OS (HR:0.47 [95%CI:0.32-0.71], P<0.001) in multivariate models. ConclusionsThe development of irAEs is associated with improved clinical outcomes to immunotherapy in patients with advanced SCLC.

Analysis of clinical features and prognostic factors of lung cancer patients: A population-based cohort study.

This paper analyses clinical features of lung cancer patients and discusses factors influencing the lung cancer occurrence and prognosis. Patients diagnosed with lung cancer from 1975 to 2016 are analysed based on SEER database. The samples are divided into groups according to the number of positive lymph nodes of LN>3 and LN≤3. Univariate and multivariate Cox risk models are performed. After balancing the clinicopathological features of the two groups with the propensity score matching (PSM) method, the survival rates of the two groups are compared. A total of 30864 patients are included in this study. Kaplan-Meier curves show that the survival rate of patients with LN≤3 is higher than that of patients with LN>3 (P<0.0001). Univariate and multivariate Cox proportional risk model analysis suggests that the number of lymph nodes is an independent prognostic risk factor for lung cancer. LN≤3 group shows better OS (HR2.066; 95% CI 1.941-2.199, P<0.01) and better CSS (HR 2.461; 95% CI 2.304-2.629, P<0.01). In addition, age at diagnosis, gender, Laterality, Derived AJCC T, 7th ed (2010-2015), Derived AJCC N, 7th ed (2010-2015) and Derived AJCC M, 7th ed, (2010-2015) have also been proved to be potential prognostic factors. A total of 1,851 pairs of patients are screened after 1:1 PSM matching. Patients with LN≤3 have significant improvements in OS and CSS (HR 1.09; 95% CI 1.001-1.187, P<0.05 and HR 1.127; 95% CI 1.03-1.232, P<0.001). The number of lymph nodes is an independent prognostic risk factor for lung cancer. Patients with fewer lymph node positives have a better survival prognosis than patients with more lymph nodes.

Real-world outcomes of patients with BRAF-mutated mCRC treated in the United States.

4030 Background: BRAF mutations portend a poor prognosis in metastatic colorectal cancer (mCRC). Recent trials have hypothesized that using more aggressive triplet-based chemotherapy regimens such as FOLFOXIRI in the frontline setting may improve outcomes in this patient population. In this study, we utilized real-world data to assess whether FOLFOXIRI is being used in the United States (US) and compared survival outcomes in BRAF mutated (BRAFmt) mCRC stratified by first line (1L) therapy. Methods: The nationwide Flatiron Health EHR-derived de-identified database was reviewed for patients diagnosed with mCRC between 2013 and 2018. Patients who had documented BRAF mutation testing and received a standard 1L therapy were included for analysis. Patients who did not have a visit or medication order within 90 days of metastatic diagnosis were excluded to ensure patients were engaged with care at the data-providing institution. Kaplan-Meier and Cox proportional hazard modeling were used to compare survival outcomes stratified by BRAF mutation status and 1L therapy received. Results: A total of 4,454 patients with documented BRAF mutational status were included, of which 3,988 (89.5%) were BRAF wild type (BRAFwt) and 466 (10.5%) were BRAFmt. Median OS was 15.4 months (mo) in the BRAFmt group compared to 28.1 mo in the BRAFwt group (HR 0.48, 95% CI 0.41- 0.56, p &lt; 0.001). Only 3% (n = 16) of BRAFmt patients received 1L FOLFOXIRI +/- bevacizumab with a median OS of 13.8 mo compared to 15.5 mo in patients receiving a chemotherapy doublet (FOLFOX, CAPEOX, or FOLFIRI) +/- bevacizumab (95% CI 4.9 – not reached vs 14.3 – 19.0, p = 0.38). In BRAFmt patients, multivariate analysis (MVA) did not detect a significant improvement in OS with the use of FOLFIRI plus bevacizumab (HR 0.88, 95% CI 0.50-1.56, p = 0.67) or FOLFOX/CAPEOX plus bevacizumab (HR 0.89, 95% CI 0.59 – 1.34, p = 0.58) when compared to chemotherapy doublet alone. A MVA comparing 1L therapies in the BRAFwt group did not detect a significant improvement in OS with bevacizumab plus chemotherapy doublet compared to chemotherapy doublet alone. When stratified by 1L treatment regimen, similar proportions of BRAFmt patients received second line therapy. Conclusions: This analysis of real-world data confirms the negative prognostic impact of BRAF mutations in mCRC and suggests that FOLFOXIRI has not been widely adopted in the management of these patients in the US. We were unable to demonstrate any significant difference in OS of patients with BRAFmt mCRC based on type of 1L therapy received.

Final analysis of KEYNOTE-189: Pemetrexed-platinum chemotherapy (chemo) with or without pembrolizumab (pembro) in patients (pts) with previously untreated metastatic nonsquamous non-small cell lung cancer (NSCLC).

9582 Background: The phase III KEYNOTE-189 study (NCT02578680), showed significant improvements in OS and PFS with pembro + chemo vs placebo + chemo in pts with previously untreated metastatic nonsquamous NSCLC without sensitizing EGFR/ALK mutations. We report the protocol-specified final analysis of KEYNOTE-189. Methods: Pts were randomized 2:1 to receive 35 cycles of pembro 200 mg Q3W (n = 410) or placebo Q3W (n = 206) plus 4 cycles of pemetrexed (pem) and carboplatin/cisplatin followed by maintenance pem. Pts in the placebo + chemo arm could crossover to pembro upon PD. PFS and OS were primary endpoints; ORR was a secondary endpoint. PFS2 (time from randomization to objective tumor progression on next-line treatment/death), was an exploratory endpoint. Results: At data cutoff (May 20, 2019), median (range) time from randomization to data cutoff was 31.0 (26.5–38.8) mo. 17 pts in the pembro + chemo arm and 1 pt in the placebo + chemo arm were receiving initially assigned treatment; 84 pts crossed over to pembro. Median (95% CI) OS (22.0 [19.5–24.5] vs 10.6 [8.7–13.6] mo; HR 0.56 [95% CI, 0.46–0.69]) and PFS (9.0 [8.1–10.4] vs 4.9 [4.7–5.5] mo; HR 0.49 [95% CI, 0.41–0.59]) were longer with pembro + chemo vs placebo + chemo (Table). The 2-y OS rate was 45.7% vs 27.3% and the 2-y PFS rate was 22.0% vs 3.4%. ORR was 48.3% with pembro + chemo vs 19.9% with placebo + chemo. 56 pts in the pembro + chemo arm completed 35 cycles of pembro among whom ORR was 85.7% (4 CR, 44 PR, 8 SD) and median OS was not reached. 292 (72.1%) pts in the pembro + chemo arm and 135 (66.8%) pts in the placebo + chemo arm had grade 3–5 AEs. Conclusions: Pembro + chemo continued to show improved outcomes in OS, PFS, ORR and PFS2 compared with placebo + chemo, with manageable toxicity. These findings support first-line pembro + chemo in pts with previously untreated metastatic nonsquamous NSCLC. Clinical trial information: NCT02578680 . [Table: see text]

Comparison of different systemic therapeutic regimes in resectable high-risk soft tissue sarcoma: Results of a network meta-analysis.

11549 Background: The treatment of high-risk soft tissue sarcoma of the trunk or the extremities consists of surgical resection with risk-adapted radiation therapy. Further treatment options which can significantly improve local and systemic tumor control including chemotherapy are not well established. Due to the heterogeneity of disease different systemic approaches as well as their application during different time points have been attempted. Methods: We conducted a literature search for randomized clinical trials in the treatment of localized, resectable high-risk soft tissue sarcoma comparing different treatment modalities according to the PRISMA guidelines. We extracted published hazard ratios and number of events for the endpoints of overall and disease-free survival (OS; DFS) as well as local and distant recurrence-free interval (LRFI; DRFI). The different modalities were compared in a network meta-analysis against the defined standard treatment surgery ± radiotherapy using the inverse-variance heterogeneity model (ivhet) with the help of the Microsoft Excel add-in Meta-XL V5.3. Results: The literature search identified 25 studies including 3489 patients. The network analysis showed that adjuvant chemotherapy (adjCTx) results in a significant improvement in overall survival (HR = 0.86; CI-95%: 0.75-0.97; p = 0.017) compared to the standard treatment of surgery ± radiatherapy alone. Combined treatment with regional hyperthermia and neoadjuvant chemotherapy (HTx+nadjCTx) also improves OS (HR = 0.45; CI-95%: 0.20-1.00; p = 0.049). Preoperative chemotherapy alone (nadjCTx) as well as perioperative chemotherapy (periopCTx) resulted both in non-statistically significant improvements in OS (HR = 0.61; CI-95%: 0.29-1.29; p = 0.195) and (HR = 0.48; CI-95%: 0.15-1.55; p = 0.218). Histology-tailored neoadjuvant chemotherapy (tNaCTx) also showed no effect on overall survival (HR = 1.08; CI-95%: 0.45-2.61; p = 0.868). The analysis of DFS, LRFI and DRFI disclosed a similar pattern between the different treatment regimens. Conclusions: The addition of cytotoxic chemotherapy in resectable high-risk soft tissue sarcomas provides a measurable benefit in overall survival. Shifting of systemic therapy to the neoadjuvant setting and combination with regional hyperthermia might be favored. Predictive clinical and molecular markers are needed to evaluate and limit potentional risks prospectively going forward.

Durvalumab ± tremelimumab + platinum-etoposide in first-line extensive-stage SCLC (ES-SCLC): Updated results from the phase III CASPIAN study.

9002 Background: CASPIAN is an open-label, Phase 3 study of durvalumab (D) ± tremelimumab (T) + etoposide and either cisplatin or carboplatin (EP) for pts with 1L ES-SCLC. At the planned interim analysis (data cutoff Mar 11, 2019; 63% maturity), D + EP demonstrated a statistically significant improvement in OS compared with EP alone (HR 0.73 [95% CI 0.59–0.91]; p=0.0047). Here we present a planned updated analysis of OS for D + EP vs EP and the first results for D + T + EP vs EP. Methods: Treatment-naïve pts with ES-SCLC (WHO PS 0/1) were randomized 1:1:1 to D 1500 mg + EP q3w, D 1500 mg + T 75 mg + EP q3w, or EP q3w. In the IO arms, pts received 4 cycles of EP + D ± T, followed by maintenance D 1500 mg q4w until disease progression. Pts received one additional dose of T 75 mg post EP in the D + T + EP arm. In the EP arm, pts received up to 6 cycles of EP and optional PCI (investigator’s discretion). The two primary endpoints were OS for D + EP vs EP and for D + T + EP vs EP. Results: 268, 268 and 269 pts were randomized to D + EP, D + T + EP and EP, respectively; baseline characteristics were generally well balanced across arms. As of Jan 27, 2020, the median follow-up was 25.1 mo, 82% maturity. D + EP continued to demonstrate improvement in OS vs EP, with a HR of 0.75 (95% CI 0.62–0.91; nominal p=0.0032); median OS 12.9 vs 10.5 mo, respectively. 22.2% of pts were alive at 2 y with D + EP vs 14.4% of pts with EP. D + T + EP numerically improved OS vs EP, however this did not reach statistical significance per the prespecified statistical plan: HR 0.82 (95% CI 0.68–1.00; p=0.0451 [p≤0.0418 required for stat sig]); the median OS was 10.4 mo and 23.4% of pts were alive at 2 y. Secondary endpoints of PFS and ORR remained improved with D + EP vs EP and will be presented. Confirmed investigator-assessed ORR was similar for D + T + EP vs EP (58.4% vs 58.0%). Median PFS was similar for D + T + EP vs EP (4.9 mo vs 5.4 mo), but the 12-mo PFS rate was numerically higher (16.9% vs 5.3%); PFS HR 0.84 (95% CI 0.70–1.01). In the D + EP, D + T + EP and EP arms, respectively, incidences of all-cause AEs of Grade 3/4 were 62.3%, 70.3% and 62.8%; AEs leading to discontinuation 10.2%, 21.4% and 9.4%; and AEs leading to death 4.9%, 10.2% and 5.6%. Conclusions: The addition of durvalumab to EP continued to demonstrate improvement in OS compared with a robust control arm, further supporting this regimen as a new standard of care for 1L ES-SCLC offering the flexibility of platinum choice. No additional benefit was observed when T was combined with D + EP in this pt population. Safety findings in all arms remained consistent with the known safety profiles of all agents. Clinical trial information: NCT03043872.

Residual circulating tumor DNA (ctDNA) after two months of therapy to predict progression-free and overall survival in patients treated on S1403 with afatinib +/- cetuximab.

9532 Background: ctDNA from patient plasma has demonstrated diagnostic utility in non-small cell lung cancer (NSCLC). Longitudinal changes in mutant allele frequency (MAF) have great potential to refine clinical management on targeted therapies. Methods: S1403 was a first-line phase II study of afatinib w or w/o cetuximab in pts with EGFR-mutant NSCLC. Between March, 2015 and April, 2018, 174 pts were randomized with 168 determined to be eligible. The study closed early due to futility. Plasma specimens were prospectively collected at baseline, Cycle 3 Day 1 (C3D1; 8 weeks) and at progression, and processed for batch analysis of ctDNA by next-generation sequencing (Guardant 360). A complete case analysis approach was used. The Kaplan-Meier method was used to estimate survival distributions, a Cox model to estimate hazard ratios and confidence bounds, and the log-rank test to compare distributions. A landmark analysis was used to assess predictive value of ctDNA clearance at C3D1. Results: 104 patients (62%) had analyzable baseline plasma specimens available, with EGFR mutations detected in 83 (80%). PFS was significantly shorter for pts with EGFR ctDNA positivity at baseline (p = 0.03) (Table) compared to those with no detectable ctDNA, likely a prognostic effect. Kinetic changes in ctDNA MAFs were analyzed in 79 pts with matching baseline and C3D1 specimens. Of 62 cases with detectable ctDNA at baseline, 68% (42/62) became undetectable at C3D1 (“ctDNA clearance”); ctDNA clearance relative to residual ctDNA was associated with significantly longer PFS (p = 0.00001) and OS (0.003) (Table). To date, 29 pts had matching at-progression samples. T790M mutations were observed at progression in 6/29 (24%) cases. Other putative emergent resistance factors include: a TACC3-FGFR3 and an EML4-ALK fusion, MET exon 14 skipping, multiple MET amplifications and NF1 frameshift mutations. Conclusions: Clearance of EGFR ctDNA after 60 days of therapy was associated with a substantial and statistically significant improvement in subsequent PFS and OS. Incorporation of ctDNA kinetics into routine clinical care represents a promising platform to identify patients with inferior outcomes on TKIs and detect targetable emergent resistance mechanisms. [Table: see text]

IMpower150: Exploratory analysis of brain metastases development.

9587 Background: In the global phase III IMpower150 study (NCT02366143), atezolizumab (atezo) + bevacizumab (bev) + chemo (carboplatin + paclitaxel [CP] (ABCP) showed significant improvements in PFS and OS vs BCP in patients with chemotherapy-naive metastatic NSCLC (Socinski et al. N Engl J Med 2018). Because bev has been shown to delay or prevent brain metastases progression in NSCLC (Fu et al. J Chemother 2016; Ilhan-Mutlu et al. Mol Can Ther 2016), exploratory analyses were conducted to assess the development of brain metastases in patients treated with ABCP, BCP and atezo + CP (ACP) in IMpower150. Methods: A total of 1202 patients (intention-to-treat [ITT] population) were randomized 1:1:1 to receive ABCP, ACP or BCP. Doses were given every 3 weeks: atezo 1200 mg, bev 15 mg/kg, carboplatin AUC 6 mg/mL/min and paclitaxel 200 mg/m2. Co-primary endpoints were investigator-assessed PFS and OS in ITT–wild-type (no EGFR or ALK alterations) patients. Exploratory analyses included the rate and time to development (TTD) of new brain metastases in the ITT population, regardless of the presence of baseline brain metastases, as well as safety. Brain scans were performed as clinically indicated, and analyses were based on investigator assessments. Results: With a minimum follow-up of 32.4 months in the ITT population (data cutoff: September 13, 2019), 100 patients had developed brain metastases, with the highest rate of new brain lesions seen in the ACP (11.9%) vs the ABCP (7.0%) and BCP (6.0%) arms (table). Median TTD was not reached in any arm; a trend toward delayed TTD was seen in the ABCP vs BCP arm (HR, 0.68 [95% CI: 0.39, 1.19]). Among patients with and without brain metastases, 17 (35.4%) and 155 (44.0%) in the ACP arm, 18 (64.3%) and 207 (56.7%) in the ABCP arm and 10 (41.7%) and 183 (49.5%) in the BCP arm had Grade 3-4 treatment-related adverse events, respectively. Conclusions: The ACP arm had the highest rate of new brain lesions, whereas the ABCP and BCP arms had similar, lower rates. Taken together with the trend toward delayed development of new brain lesions with ABCP, the data suggest that adding atezo to BCP may not reduce the rate of new brain lesion development but may delay the time to new lesion development. No new safety signals were observed in this exploratory analysis. Clinical trial information: NCT02366143 . [Table: see text]

Germline and somatic DNA damage repair gene mutations potentially predict the efficacy of relevant treatment in Chinese patients with pancreatic ductal adenocarcinoma.

e16732 Background: PDAC is a fatal disease with molecular heterogeneity, inducing differences in biological behaviour and therapeutic strategy. We conducted a study to reveal the mutation landscape of Chinese PDAC patients, and investigate the predictive role of germline and somatic DNA damage repair (DDR) status in precise treatment. Methods: 195 PDAC patients were enrolled from multiple medical centers of China between Jan 2016 to Nov 2019. Baseline clinical or genetic characteristics, and survival status were collected. NGS were performed on paraffin-embedded resected tissues or peripheral blood using a panel of 417 genes, including 50 DDR-related genes. Survival analysis was conducted using Kaplan-Meier, and Cox proportional hazard regression model. Results: The main driver genes were KRAS, TP53, CDKN2A, and SMAD4. Patients with KRAS mutation showed worse OS than those without (p = 0.048). DDR deficiency were identified in 15.38% of overall patients, mainly occurred in BRCA2 (4.62%), ATM (4.10%), RAD50 (1.54%) and MLH1 genes (1.03%). No significant improvement of OS existed between patients with or without DDR mutations (p = 0.88). Treatment with olaparib (adjusted HR, 0.2550; P = 0.0720) or platinum-based chemotherapy (adjusted HR, 0.1308; P = 0.0185) respectively decreased hazard of death in patients with DDR mutation. Besides BRCA gene, ATM mutant patients treated with olaparib harbored prolonged median OS than those without olaparib treatment (22.25 vs 15.2 month). Despite a little higher PD-L1 expression rate were seen in DDR mutant patients (29.17% vs 20.51%), no statistical correlation between tumor mutation burden level and DDR mutation was identified. And in patients treated with PD-1 blockade, 2 patients of DDR wild-type group both had SD, whereas of the remaining 5 patients with DDR deficiency, 1 was evaluated as PR, 3 as SD, and 1 as PD (ORR, 0 wt vs 20% mut). Conclusions: In this multi-center retrospective study, we deciphered the intra-tumoral genetic heterogeneity in Chinese PDAC population, which differs from western patients cohort to some extent. We found the potential role of germline and somatic DDR mutation status in predicting the response to olaparib and platinum-based chemotherapy, especially with BRCA or ATM mutation. However, DDR alteration was limited in prediction of hypermutational status and sensitivity to PD-1 blockade. Our study may provide a valuable evidence for clinical application of DDR mutation as a potential biomarker for precise treatment.

A systematic review and network meta-analysis of adjuvant therapy for curatively resected biliary tract cancers.

Recent randomized controlled trials (rcts) have contributed high-quality data about adjuvant therapy in curatively resected biliary tract cancer (btc); however, a standard approach to treating those patients still has not been developed. We conducted a systematic review of published studies and abstracts up to and including June 2018, choosing rcts involving patients with btc receiving adjuvant chemotherapy after complete surgical resection. Network meta-analysis methods were used for indirect comparisons of overall survival (os) and relapse-free survival (rfs) for various adjuvant therapies. Five rcts were included in qualitative synthesis, and three rcts (bilcap, prodige 12-accord 18, and bcat) had data sufficient for inclusion in the meta-analysis. Results from the indirect comparison demonstrated no significant improvement in os for capecitabine compared with gemcitabine or with gemcitabine-oxaliplatin (gemox), the hazard ratios (hrs) being 0.82 [95% confidence interval (ci): 0.53 to 1.27] and 0.86 (95% ci: 0.56 to 1.34) respectively. Similarly, no significant improvement in rfs was observed for capecitabine compared with gemcitabine or gemox. Although in the present analysis, we found no statistically significant improvements in os or rfs for capecitabine compared with gemox or gemcitabine, capecitabine can-until further prospective trials are completed-be considered the standard of care in the adjuvant setting based on a single randomized phase iii study.

Allogeneic Hematopoietic Cell Transplantation for Adult Acute Lymphoblastic Leukemia: Significant Increase in Survival in the Post-Targeted Immunotherapy Era

Background The management of adult acute lymphoblastic leukemia (ALL) has evolved over the last five years with the FDA approval of targeted immunotherapies, routine incorporation of minimal residual disease, and uptake of the pediatric regimen in young adults. However, allogeneic hematopoietic cell transplantation (HCT) remains an important treatment modality for this population and progress has concomitantly occurred in the field of HCT. We hypothesized that a combination of these advancements would translate into significant improvements in post-HCT survival in adult ALL. Methods Successive patients >= 18 years who had undergone first allogeneic HCT for ALL at Stanford University between January 1, 2005 and January 30, 2019 were included and were categorized as Cohort 1 or Cohort 2 based upon time period of HCT: 2005-2013 vs 2014-2019, respectively. For survival analyses, patient post-HCT follow-up times in Cohort 1 were truncated to the maximum follow-up time in Cohort 2 (approximately 5 years) in order to account for differences in long-term follow-up between the cohorts. Results 308 adults (163 in Cohort 1; 145 in Cohort 2) with ALL underwent HCT. The median follow-up from HCT was 738 and 588 days in Cohorts 1 and 2, respectively. Median age was 39 years (range, 19-70) and did not differ between groups; 50-55% were men and 30-35% were Hispanic across time periods. Most patients (79-85% across time periods) received myeloablative conditioning (MAC) with a TBI-based regimen; a slight increase in non-TBI based MAC was observed in Cohort 2. Relative to Cohort 1, patients transplanted in Cohort 2 received cord blood units more frequently and were also more likely to enter HCT in CR1. The estimated six month, one, and two-year HCT outcomes are depicted in Table 1. The 2-year cumulative incidence of relapse (31% vs 25%) and TRM (23% vs 17%) were not significantly different between the two time cohorts but trended in favor of Cohort 2. Significant improvement in OS following HCT was observed in Cohort 2 (Figure 1) with estimated 2-year OS of 51% vs 70% in Cohorts 1 and 2, respectively. Conclusions In this large single center analysis of adult ALL outcomes following HCT over time, we demonstrate that OS following HCT has substantially improved since 2014, coinciding with a number of advancements in the fields of ALL and HCT. These data, if confirmed in a multi-center analysis, should provide new benchmarks for outcomes following HCT in adult ALL.

BT-02 MULTIDISCIPLINARY TREATMENT FOR EPENDYMOMA

BACKGROUNDIn intracranial ependymoma, the effectiveness of chemotherapy and radiation therapy is unclear, and the degree of tumor removal contributes to the improvement of life prognosis. Methods: We examined ependymoma cases treated in our institution from July 1998 to March 2017.RESULTSThere were 18 boys and 7 girls. The average age at the time of surgery is 5.3 ± 3.6 years. The pathological diagnosis was Grade II for 8 cases and Grade III for 17 cases. Genetic analysis was performed in 16/25 cases (64%). Of the infratentorial cases, 10/11 cases (90.1%) were PFA and PFB were one case. Of the supratentorial cases, 3/5 cases (60%) were positive for RELA fusion. As chemotherapy, 19 patients were VCR + VP-16 + CDDP + CPA. Irradiation was performed in all cases, local irradiation (50.4–55.8Gy) in 22 cases (88%), and craniospinal irradiation in 2 cases (8%). The 7-year OS was 74.6 ± 9% and the 7-year PFS was 59.7 ± 10.5%. Grade III showed a short OS (p = 0.053). GTR and NTR were obtained in the first excision in 14 cases (56%), and OS and PFS were not significantly different from those in the STR group (p = 0.219, p = 0.248). GTR and NTR including 2nd-look surgery were obtained in 18 cases (72%), and significant improvement of OS was observed compared with STR group (p = 0.02). In patients with hydrocephalus preoperatively, OS tended to be short (p = 0.057), especially in cases requiring VP shunt placement, OS was significantly shortened (p = 0.017).CONCLUSIONEven if it is not GTR or NTR at the first operation, improvement of OS is expected by total excision after chemotherapy. The importance of chemotherapy was suggested to be suppression of tumor growth until reoperation and reduction of blood loss during surgery.

Abstract B36: Maintenance chemotherapy after chemoradiation in patients with locally advanced pancreatic cancer

Abstract Background: More than half of patients (pts) with pancreatic cancer (PC) initially present with unresectable, locally advanced disease (LAPC). Data on management of these pts after systemic chemotherapy are scarce. Many clinicians utilize a strategy of induction chemotherapy followed by consolidative concurrent chemoradiation (CRT) for pts not progressing on initial chemotherapy. How to manage pts after CRT is controversial. We sought to evaluate the role of maintenance chemotherapy (MCT) after CRT in pts with LAPC. Methods: We retrospectively analyzed LAPC pts treated with CRT at MD Anderson from 2005-2018. Pts who were taken for curative-intent surgery were excluded. Primary and secondary outcomes were median progression-free survival (mPFS) and median overall survival (mOS), respectively, as measured from the start date of CRT. Data were also obtained on pt demographics, response, and duration of induction chemotherapy as well as MCT regimens. Results: We included 165 pts with LAPC treated with CRT in our analysis. Median age was 66 (range 39 – 84), and 97 (59%) pts were male. Median follow-up was 12.9 months. The median duration from initiation of induction chemotherapy to start of CRT was 4.4 months. Most pts (84%) received 1 line of induction chemotherapy prior to CRT. Ten pts (6%) did not receive induction chemotherapy and 17 pts (10%) received at least 2 lines prior to CRT. All but 9 pts (94%) developed disease progression (PD) after CRT, and 49 pts (33%) had PD within 3 months of CRT. On univariate analysis, PD on the induction chemotherapy regimen immediately prior to CRT was associated with shortened PFS (HR 2.46, p &amp;lt; 0.001) and OS (HR 2.96, p &amp;lt; 0.001) after CRT. Most pts (78%) did not receive MCT after CRT. 69% of pts who received MCT were male, compared to 56% of those who did not receive MCT. The percentages of pts who had PD on the chemotherapy regimen immediately prior to CRT in the MCT and no-MCT groups were 9% and 12%, respectively. Sixteen pts who received MCT were treated with either gemcitabine alone or a gemcitabine-containing regimen, while 14 pts received capecitabine monotherapy. On univariate analysis, the use of MCT after CRT was associated with prolonged mPFS (9.0 vs. 4.2 months, p = 0.01), but was not associated with an increase in mOS (15.5 vs. 12.5 months, p = 0.14). On multivariable analysis controlling for race, radiation dose, age, and whether there was progression on the chemotherapy regimen prior to CRT, the use of MCT was significantly associated with both prolonged PFS (HR 0.45, p &amp;lt; 0.001) and OS (HR 0.66, p = 0.047). Conclusions: In this single-institution retrospective analysis of 165 pts with LAPC treated with CRT, treatment with post-CRT MCT was associated with a significant improvement in both PFS and OS as measured from the start date of CRT. Based on these results, MCT may be an appropriate option for pts with LAPC who have not progressed following consolidative CRT, and a prospective trial should be performed to better address this knowledge gap. Citation Format: Jonathan D. Mizrahi, Shalini Moningi, Graciela M. Nogueras-Gonzalez, Robert A. Wolff, Milind M. Javle, Gauri R. Varadhachary, Linus Ho, David R. Fogelman, Kanwal P. Raghav, Michael J. Overman, Christopher H. Crane, Joseph M. Herman, Albert C. Koong, Eugene J. Koay, Jane E. Rogers, Shubham Pant. Maintenance chemotherapy after chemoradiation in patients with locally advanced pancreatic cancer [abstract]. In: Proceedings of the AACR Special Conference on Pancreatic Cancer: Advances in Science and Clinical Care; 2019 Sept 6-9; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2019;79(24 Suppl):Abstract nr B36.

LBA3 Nivolumab (NIVO) + platinum-doublet chemotherapy (chemo) vs chemo as first-line (1L) treatment (tx) for advanced non-small cell lung cancer (aNSCLC): CheckMate 227 - part 2 final analysis

LBA3 Nivolumab (NIVO) + platinum-doublet chemotherapy (chemo) vs chemo as first-line (1L) treatment (tx) for advanced non-small cell lung cancer (aNSCLC): CheckMate 227 - part 2 final analysis