bluuebunny/crossref_metadata_2025_split huggingface dataset:
Randomized phase III study comparing carboplatin plus pemetrexed followed by pemetrexed versus docetaxel in elderly patients with advanced non-squamous non-small-cell lung cancer (JCOG1210/WJOG7813L).
Authors: Okamoto Isamu , Nokihara Hiroshi , Yoh Kiyotaka , Sugawara Shunichi , Horinouchi Hidehito , Azuma Koichi , Yoneshima Yasuto , Murakami Haruyasu , Daga Haruko , Hosomi Yukio , Atagi Shinji , Ozaki Tomohiro , Horiike Atsushi , Fujita Yuka , Okamoto Hiroaki , Ando Masahiko , Nomura Shogo , Yamamoto Nobuyuki , Ohe Yuichiro , Nakagawa Kazuhiko 
Published: March 2020

9031 Background: The aim of this phase III randomized trial is to determine the efficacy of pemetrexed and carboplatin followed by pemetrexed for elderly patients (pts) with advanced non-squamous non-small-cell lung cancer (NSCLC). Methods: Cytotoxic chemotherapy-naïve, ECOG-PS 0-1, aged 75 years or older, and advanced stage non-squamous NSCLC pts were randomized to receive either docetaxel 60 mg/m2 on day 1 every 3 weeks [DOC] or carboplatin AUC 5 mg/ml/min and pemetrexed 500 mg/m2 on day 1 every 3 weeks followed by maintenance therapy with pemetrexed 500 mg/m2 every 3 weeks after 4 cycles of carboplatin and pemetrexed [CBDCA/PEM] given until disease progression or unacceptable toxicities. The primary endpoint was OS. Non-inferiority of CBDCA/PEM arm was planned to be demonstrated if upper limit of 95% confidence interval (CI) for hazard ratio (HR) did not exceed 1.154. Results: Between August 2013 to February 2017, 433 pts with a median age of 78 years (range, 75 to 88) were randomly assigned to the DOC arm (n = 217) or the CBDCA/PEM arm (n = 216). Non-inferiority of CBDCA/PEM arm was confirmed in all enrolled patients (HR for OS, 0.850; 95% CI, 0.684 to 1.056, P < 0.01). The median OS for DOC and CBDCA/PEM arms were 15.5 months and 18.7 months, respectively. In the CBDCA/PEM arm, PFS was significantly better (HR, 0.739; 95% CI, 0.609 to 0.89) and response rate was better (28.2% vs. 36.8%; P = 0.07), and incidence of neutropenia or febrile neutropenia of grade 3 or 4 was significantly lower. Grade 3 or 4 thrombocytopenia or anemia was more common in the CBDCA/PEM arm. Four treatment-related deaths (two in each treatment arm) occurred. QOL (FACT-LCS) was favorable for CBDCA/PEM arm throughout 18 weeks after enrollment. Conclusions: Pemetrexed/carboplatin followed by pemetrexed maintenance is a valid therapeutic option for the first-line treatment of elderly pts with advanced non-squamous NSCLC. Clinical trial information: 000011460.
SHERLOC: A phase 2 study of MM-121 plus with docetaxel versus docetaxel alone in patients with heregulin (HRG) positive advanced non-small cell lung cancer (NSCLC).
Authors: Sequist Lecia V. , Janne Pasi A. , Huber Rudolf M. , Gray Jhanelle Elaine , Felip Enriqueta , Perol Maurice , Hirsch Fred R. , Tan Daniel Shao-Weng , Kuesters Geoffrey , Zalutskaya Alena , Santillana Sergio , Pipas J. Marc , Shepherd Frances A. 
Published: March 2020

9036 Background: Seribantumab (MM-121) is a human monoclonal IgG2 antibody that blocks the HRG domain of HER3. Preclinical data suggest that seribantumab reverses HRG mediated drug resistance across multiple cancer models. In prior retrospective analyses, addition of seribantumab to standard of care (SOC) appeared to improve outcomes in pts with HRG+ tumors. Here we tested if seribantumab plus SOC improved progression-free survival (PFS) in pts with HRG+ lung adenocarcinoma who had received prior platinum-based therapy. Methods: SHERLOC was a randomized, open-label, multicenter, Phase 2 study in pts with advanced HRG+ adenocarcinoma of the lung. Archival or pre-treatment tumor samples were assessed for HRG+ by RNA in situ hybridization. Eligibility criteria included prior platinum-based therapy for advanced disease with ≤ 2 total prior lines of therapy (prior IO was allowed) and no EGFR or ALK mutations. Pts were randomized 2:1 to receive seribantumab 3000 mg/docetaxel 75 mg IV q3w (experimental; exp) or docetaxel 75 mg IV q3w alone (control). Primary endpoint was PFS. Key secondary endpoints were overall survival (OS), objective response rate (ORR), and adverse event (AEs) profile. Results: At a pre-specified interim analysis of 75% of total PFS events, 108 pts were enrolled (exp n = 71, control n = 37). Median age was 62y (range 34-83y); female 34%; one prior treatment only 39%. Median PFS was 3.0m for exp and 4.0m for control, HR = 1.66m (p = 0.084). Median OS was 7.9m for exp and 8.4m for control, HR = 1.50 (p = 0.235). ORR was 19.7% for exp and 5.6% for control (p = 0.052). Serious AEs were more frequent in the exp arm (40.8%) vs control (24.3%). Most common treatment emergent AEs (TEAEs) in the exp arm were diarrhea (47%), fatigue (37%), and neutropenia (27%). Based on a determination of futility at interim analysis, the study was terminated early. Conclusions: Seribantumab failed to improve PFS when added to docetaxel among previously treated advanced HRG+ NSCLC pts. A higher response rate and a higher incidence of TEAEs were observed in the exp arm. No further study of seribantumab is planned in NSCLC. Clinical trial information: NCT02387216.
Patient-reported outcomes (PROs) with first-line durvalumab (D) ± tremelimumab (T) versus chemotherapy (CT) in metastatic NSCLC: Results from MYSTIC.
Authors: Garon Edward B. , Cho Byoung Chul , Reinmuth Niels , Lee Ki Hyeong , Luft Alexander , Ahn Myung-Ju , Robinet Gilles , Le Moulec Sylvestre , Natale Ronald , Schneider Jeffrey Gary , Shepherd Frances A. , Garassino Marina Chiara , Geater Sarayut Lucien , Papai-Szekely Zsolt , Van Ngoc Tran , Liu Feng , Scheuring Urban J. , Rydén Anna , Peters Solange , Rizvi Naiyer A. 
Published: March 2020

9048 Background: MYSTIC, an open-label, Phase 3 trial of first-line D (anti-PD-L1) ± T (anti-CTLA-4) vs platinum CT in mNSCLC, showed an improvement in overall survival (OS) with D vs CT in pts with tumor cell PD-L1 expression ≥25% (TC ≥25% [primary analysis population]; D vs CT, HR 0.76 [97.54% CI 0.56–1.02], p = 0.036; D+T vs CT, HR 0.85 [98.77% CI 0.61–1.17], p = 0.202). Here we summarize PROs from MYSTIC. Methods: Immunotherapy/CT-naïve mNSCLC pts were randomized (1:1:1) to D, D+T, or CT. Symptoms, function, and global health status/quality of life (QoL) were assessed using the EORTC QLQ-C30 v3 questionnaire and its lung cancer module, QLQ-LC13. A change in score from baseline ≥10 points was predefined as clinically meaningful (CM). Mean changes from baseline (over 12 mos) for prespecified symptoms were analyzed using a mixed model for repeated measures (MMRM). Time from randomization to the first CM deterioration (TTD) was analyzed. Results: Among pts with PD-L1 TC ≥25% (n = 488), there were no differences between arms in symptoms, function, or global health status/QoL at baseline. Compliance with completing the questionnaires was ≥60% to wk 120 in the D±T arms, and to wk 40 (C30) and wk 44 (LC13) in the CT arm. MMRM analysis showed significant between-arm differences in changes from baseline in favor of D for fatigue (difference vs CT −9.5) and appetite loss (−11.9; CM), and D+T for fatigue (−11.7; CM). Significantly longer TTD (median, mos) was seen with D and D+T vs CT for appetite loss (12.8 and 5.6 vs 4.5), constipation (14.6 and 9.0 vs 5.5), nausea/vomiting (16.7 and 9.7 vs 4.5), and dyspnea (10.6 and 7.4 vs 5.6); D vs CT for diarrhea (16.3 vs 9.0), insomnia (9.3 vs 6.2), and hemoptysis (not reached vs 10.3); and D+T vs CT for fatigue (5.6 vs 2.0). Significantly longer TTD (median, mos) was also seen with D and D+T vs CT for function (cognitive [9.1 and 6.6 vs 5.2], physical [9.0 and 7.4 vs 4.2], role [D vs CT only; 7.3 vs 3.7], social [12.9 and 5.4 vs 5.2]), and global health status/QoL (5.9 and 6.8 vs 5.5). Conclusions: Pts with PD-L1 TC ≥25% treated with D±T had a reduced symptom burden over time and longer TTD for symptoms, function, and global health status/QoL compared to pts receiving CT. Clinical trial information: NCT02453282.
Evaluation of clonal hematopoiesis in late stage NSCLC using a next-generation sequencing panel targeting cancer genes.
Authors: Yaung Stephanie J. , Fuhlbrück Frederike , Wu Johnny , Casey Fergal , Peterson Maureen , Zou Wei , Palma John F. , Patil Namrata S. , Jiang Yuqiu 
Published: March 2020

9050 Background: Somatic mutations derived from the expansion of clonal populations of blood cells (clonal hematopoiesis of indeterminate potential, or CHIP) may be detected in sequencing of cell-free DNA (cfDNA) samples. We evaluated the potential implications of CHIP in targeted sequencing of lung cancer plasma samples using matched peripheral blood mononuclear cells (PBMC) to identify CHIP. Methods: Samples were evaluated from OAK, a phase 3 trial of atezolizumab in locally advanced or metastatic NSCLC following failure with platinum-based therapy. 94 samples from Cycle 1 Day 1 (C1D1) plasma and matched PBMC were analyzed with the AVENIO ctDNA Surveillance Kit (For Research Use Only, not for use in diagnostic procedures), a 198-kb next-generation sequencing panel targeting cancer genes. Plasma samples from subsequent cycles of therapy (C2D1, C3D1, and C4D1) were also sequenced with the same panel. Using median input amounts of 22.8 ng cfDNA and 50 ng PBMC DNA, we obtained median deduplicated depths of 5413 and 5070, respectively. Results: In C1D1 cfDNA, a median of 120 single nucleotide variants were detected per sample, with 5.13% of variants not identified in matched PBMC (i.e., putative tumor-derived somatic variants) versus 94.87% of variants identified in matched PBMC (i.e., germline or CHIP variants). While the majority of PBMC-matched variants were SNPs with allele frequency (AF) around 50% or 100% as expected, there was a median of 1 (range 0-8) PBMC-matched cfDNA variants per sample with AF below 10%. Consistent with CHIP, the number of PBMC-matched cfDNA variants per subject below AF 10% were positively associated with age (p-value = 0.0145), and TP53 was the most frequently mutated gene. We found similar results in plasma samples from subsequent cycles. Conclusions: Plasma and PBMC sequencing analysis identified potential mutations derived from CHIP. However, 39% of cfDNA samples had zero potential CHIP mutations identified in the study, possibly due to the specific regions targeted by the AVENIO assay. While this study suggests that only a small percentage of variants detected by the AVENIO Surveillance panel in lung cancer are derived from CHIP, further studies are warranted to assess the impact and removal of these variants.
Tracking plasma KRAS mutations (mu) in lung adenocarcinoma (LUAC) patients (p) and branching evolution.
Authors: Bracht Jillian , Karachaliou Niki , Lanman Richard B. , Dix Daniel , Faull Iris , Nagy Rebecca , López Noemí , Palmero Ramon , Viteri Ramirez Santiago , Majem Margarita , Taus Alvaro , Carcereny Costa Enric , Garde Javier , Riva Francois , Malfettone Andrea , Sampayo Miguel , Drozdowskyj Ana , Felip Enriqueta , Rosell Rafael 
Published: March 2020

9055 Background: KRAS m in LUAC p are recalcitrant to therapy. In mice models and p, STK11 m confer poor prognosis. Patients with KRAS, or KRAS with TP53 m, benefit from immunotherapy (IO). We used a cell free DNA (cfDNA) sequencing platform to sub-group 53 LUAC p with KRAS m from the Spanish Lung Liquid versus Invasive biopsy Program (SLLIP, NCT03248089), according to the coexistence of TP53 and STK11 m. We evaluated the treatment outcome in the KRAS subgroups and we explored the mutational evolution at 2 weeks (w), and at the end of the study (EOS). Methods: SLLIP was a multi-center observational study in patients with treatment-naïve metastatic LUAC. Genotyping, with a clinically validated cfDNA assay (Guardant360) was performed at 3 time points: before start of treatment, at 2 w, and upon progression or at 12 months (mo). Oncoprints were constructed based on mutation status and variant allele frequency (VAF). Results: 53 p with KRAS alterations were included. 36 male; median age 59; 46 current/ex-smokers; 64% received 1st line platinum-based chemotherapy (CT), 4% platinum-based CT+IO, 8% platinum-based CT plus bevacizumab, and 24% other or no therapy. 13 p had only KRAS m (K-only group), 25 p had KRAS + TP53 m (KP group), and 15 p had KRAS + STK11 with or without TP53 m (KS group). Median progression-free survival was 3.5 mo for all 53 p, 4.8 mo for the K-only group, 4.4 mo for the KP group, and only 2.6 mo for the KS group (p = 0.05 for KS versus K-only). The average VAF for K-only, KP, and KS groups at EOS were 6.4%, 9.7%, and 46%, respectively. When looking at p with cfDNA analysis at the three time points, the following were observed: In the K-only group, 25% lost KRAS m at 2 w and 50% at EOS. 50% and 75% gained TP53 m, at 2 w and EOS, respectively. None gained STK11 at the 2 time points. In the KP group, 40% lost KRAS m at 2 w but all had KRAS m at EOS. 20% and 10% lost TP53 m, at 2 w and EOS, respectively. 10% gained STK11 m at the 2 time points. In the KS group, 33% lost KRAS m at the 2 time points. All and 33% lost STK11 m at 2 w and EOS, respectively. 66% gained TP53 at the 2 time points. Conclusions: Subgroups of KRAS m traced in cfDNA confirm dismal prognosis to 1st line therapies. These findings prompt us to tailor IO for K-only or KP subgroups. For p with STK11 m, restoration of the STK11 function is warranted. Clinical trial information: NCT03248089.
Impact of time to treatment initiation (TTI) on survival of patients with newly diagnosed non-small cell lung cancer (NSCLC).
Authors: Azzouqa Abdel-Ghani , Chen Ruqin , Lou Yanyan , Ailawadhi Sikander , Manochakian Rami 
Published: March 2020

9058 Background: Lung Cancer is the leading cause of cancer related deaths in the USA. NSCLC comprises about 85% of lung cancer cases. Although timeliness of care in patients with NSCLC is considered an important aspect of quality care, there are conflicting data about its impact on clinical outcomes. The primary objective of this study is to determine if there is an association between TTI and survival in patients with NSCLC. Methods: In this retrospective study, we reviewed data from our multi-site Mayo Clinic Cancer Center registry and identified patients with newly diagnosed NSCLC from 2000 to 2016. TTI was calculated from time of diagnosis to time of first treatment (surgery, radiation therapy or systemic therapy). Analyses were performed by SAS software 9.4. Log-Rank test was used to compare survival. Cox regression multivariate model was used to evaluate the prognostic value of variables to survival. Results: 10010 patients (53% males and 47%) were reviewed. Median age at diagnosis was 70. Median TTI was 12 days for stage I, and 20 days for stage II, III and IV. We compared outcomes of patients with TTI > 20 days to TTI ≤20 days. Outcomes were stratified based on age, gender, grade, and stage. Median Overall Survival (OS) was significantly better for patients with TTI ≤20 days compared to TTI > 20 days (39.1 vs 28.6 months P-value < 0.0001). Further stratification, based on stage, showed significantly better OS for stage I and II patients with TTI ≤20 days compared to TTI > 20 days (103.4 vs. 63.9 months P-value < 0.0001 and 72.3 vs. 46.8 months P-value 0.0014 respectively). OS for stage III patients with TTI ≤20 days was not significantly different from patients with TTI > 20 days (30.6 vs. 28.5 months P-value 0.118). Interestingly, stage IV patients had worse OS if TTI ≤20 days compared to TTI > 20 days (8.3 vs. 12.8 months P-value < 0.0001). Conclusions: Our study showed an association between TTI and survival of patients with NSCLC. Shorter TTI was associated with better survival in stage I and II patients and worse survival in stage IV patients. Our study further highlights the controversy surrounding the topic of impact of timeliness of care on survival in patients with cancer, specifically NSCLC across different stages.
Identification and use of treatment (tx) options in patients (pts) with advanced non-small cell lung cancer (aNSCLC) after comprehensive genomic profiling (CGP): A real-world study.
Authors: Mascaux Celine , Bubendorf Lukas , Barlesi Fabrice , Clendening James W. , Zhang Qing , Mace Kieran , Gondos Adam , Foser Stefan , Wang Lisa I. , Paz-Ares Luis G. 
Published: March 2020

9076 Background: The number of targeted txs for NSCLC is increasing. By analyzing numerous molecular alterations, CGP may open more targeted tx options than single biomarker testing. Methods: We analyzed a database linking Flatiron Health electronic health record-based clinical and Foundation Medicine, Inc. (FMI) CGP genomic alteration (GA) data in US pts diagnosed from 1/2011 with aNSCLC, primarily from community practices, and with follow-up through 6/2018. We examined the prevalence and distribution of genomic findings, and agreement between tx received and CGP-directed tx options (approved for aNSCLC/other tumors) on the FMI report as a measure of clinical utility. The latter was evaluated in a subset of pts with sufficient tx and follow-up data after FMI testing. Results: Among 5112 FMI-tested pts (first test observed 8/2012), 49% had their FMI test before starting any line of tx, 97% had ≥ 1 GA with known/likely function (median = 5), and 85% had ≥ 1 potential tx option (52% had ≥ 1 option for aNSCLC and 33% had ≥ 1 for another tumor type only). In 1366 pts evaluable for tx agreement after FMI testing, 572 (42%) received a tx listed on the FMI report and 111 (8%) were enrolled in clinical trials. Pts with a tx option approved for aNSCLC were more likely to have a tx agreeing with an option on the FMI report (67% of 754) v pts with a tx option approved in another tumor type only (8% of 612). Among the 1366 pts, 14% had EGFR/ALK/ROS1/BRAF (EARB) tx options only. The remaining 1170 had a non-EARB tx option, either as their only option (1014; 87%), or in addition to an EARB tx option (156; 13%). The non-EARB tx options included 377 pts (32%) with a tumor mutational burden-associated tx option. In these 1170 pts, 341 (29%) had an agreeing tx besides EARB, and 100 (9%) were enrolled on trials. Conclusions: FMI CGP identified potential NSCLC-specific tx options/a clinical trial opportunity for 52% of pts with aNSCLC. Of the pts evaluated for tx agreement, almost ½ received a tx agreeing with an option on the FMI report and/or were enrolled in a clinical trial. FMI CGP adds value beyond single biomarker testing by identifying txs and trial options in a meaningful proportion of pts.
Quantification of circulating free and circulating tumor DNA in pretreated EGFR mutant NSCLC to inform patient outcomes.
Authors: Pender Alexandra , Hughesman Curtis , Law Elaine , Kristanti Amadea , McNeil Kelly , Tucker Tracy , Bosdet Ian , Young Sean , Laskin Janessa J. , Karsan Aly , Yip Stephen , Ho Cheryl 
Published: March 2020

9080 Background: EGFR T790M testing is standard of care for EGFR mutant (EGFRm) NSCLC progressing on 1st/2nd generation TKIs to select patients for osimertinib. Circulating free DNA (cfDNA) levels are measured prior to circulating tumour DNA (ctDNA) testing using droplet digital PCR (ddPCR) to measure activating/resistant EGFR mutations. We reviewed cfDNA levels and ctDNA mutational status to determine the influence on patient outcome. Methods: Following extraction of cfDNA from plasma using the QIAamp Circulating Nucleic Acid Kit, cfDNA levels are measured with a Qubit 2.0 Fluorometer. Custom ddPCR assays were used to test for the appropriate EGFR activating mutation and the EGFR T790M resistance mutation using the Bio-Rad QX200 system. The custom designed ddPCR assays have a limit of detection of < 0.1% variant allele fraction. All patients undergoing ctDNA testing from February-December 2018 were identified. Baseline characteristics and follow up data were collected retrospectively. OS was calculated from date of metastatic diagnosis to death/last follow-up. Results: 142 patients with EGFR mutant adenocarcinoma had EGFR ctDNA testing: results 52% indeterminant, 32% T790M, 16% activating EGFRm only. At the time of testing: median age 66, 64% female, 57% never smokers 53% Asian; systemic treatment (tx) 62% first line only, 25% two lines and 13% ≥ three lines. First TKI therapy: 32% afatanib, 66% gefitinib, 2% erlotinib. Median cfDNA concentration was 5.65 ng/ml (range 0.50-217.72). The 5 yr OS was 72% below cfDNA median and 25% above the median. Tx after ctDNA testing for below and above cfDNA median: 52 vs 33% original TKI, 34 vs 55% osimertinib, 14 vs 12% other systemic tx. Multivariate analysis shows that even accounting for age, sex and ctDNA mutation result, cfDNA concentration remains an independent predictor of outcome (HR 2.36, 95% CI 1.08-5.18, p = 0.032). Conclusions: cfDNA concentration can predict patient outcome in patients with EGFR mutant NSCLC progressing on TKI regardless of ctDNA testing results. Clinicians may consider switching to chemotherapy for patients with high cfDNA and without detectable EGFR T790M ctDNA to avoid missing the window for therapy instead of awaiting repeat EGFR T790M testing
Impact of KRAS allele subtypes and concurrent genomic alterations on clinical outcomes to programmed death 1 axis blockade in non-small cell lung cancer.
Authors: Ricciuti Biagio , Recondo Gonzalo , Umeton Renato , Nishino Mizuki , Sholl Lynette M. , Awad Mark M. 
Published: March 2020

9082 Background: Immune checkpoint inhibitors (ICI) treatment can result in durable responses for KRAS-mutant (mut) non-small cell lung cancer (NSCLC). The impact of KRAS allele subtypes and concurrent genomic alterations on ICIs efficacy is unknown. Methods: We collected clinicopathologic and genomic data from patients (pts) with advanced NSCLC treated with programmed death (PD)-1 axis inhibition at the Dana-Farber Cancer Institute. We evaluated outcomes to ICIs according to KRAS mut alleles and concurrent STK11 and KEAP1 mut. Results: Of 617 ICI-treated NSCLCs, 181 (29.3%) had KRAS mut. Median TMB (mTMB) and median PD-L1 tumor proportion score (TPS) were similar between KRAS mut and KRAS wild type (wt) tumors. Among tumors with KRAS codon 12 mut, mTMB was higher in G12V (n = 37, 12.2 mut/Mb) compared to G12C (n = 84, 11.4 mut/Mb), G12D (n = 20, 9.4 mut/Mb) and G12A (n = 13, 10.1 mut/Mb), P = 0.05. Tumors with KRAS transversions (Tv) (n = 156) had higher mTMB compared to those with KRAS transitions (Ti) (n = 25) (10.9 vs 7.6 mut/Mb, P = 0.03). Median PD-L1 TPS was similar across KRAS mut alleles. Pts with KRAS G12V had longer median progression-free survival (mPFS) (5.5 vs 2.7 months, HR:0.62 [95%CI:0.40-0.96], P = 0.03) and overall survival (mOS) (17.5 vs 9.7 months, HR:0.62 [95%CI:0.36-0.99], P = 0.05), compared to non-G12V. Pts with KRAS Tv had longer mPFS and mOS compared to pts with Ti (mPFS: 3.4 vs 2.0 months, HR: 0.58 [95%CI:0.37-0.92], P = 0.02; mOS: 10.9 vs 5.4 months, HR:0.59 [95%CI:0.35-0.99], P = 0.048). Clinicopathologic features and STK11/KEAP1 mut were balanced across all KRAS mut alleles. Among KRAS mut pts, those with KEAP1 (n:52) and STK11 (n:50) concurrent mut had shorter mPFS (KEAP1 mut 1.8 vs. KEAP1 wt 4.1 months, HR: 0.55 [95%CI:0.38-0.80], P = 0.002; STK11 mut 1.8 vs STK11 wt 4.6 months, HR:0.46 [95%CI:0.32-0.67], P < 0.0001) and mOS (KEAP1 mut 4.8 vs KEAP1 wt 15.1 months, HR: 0.51 [95%CI:0.34-0.76], P = 0.001; STK11 mut 4.8 vs STK11 wt 13.6 months, HR:0.51 [95%CI:0.34-0.76], P = 0.001). KEAP1 and STK11 mut did not impact outcome in KRAS wt pts. Conclusions: KRAS allele subtypes and concurrent genomic alterations impact ICI efficacy in NSCLC.