All times are listed in CEST (Central European Summer Time)
- N. Singh (Chandigarh, India)
- F. Lopez-Rios (Madrid, Spain)
7MO - Sotorasib in KRAS G12C–mutated advanced non-small cell lung cancer (aNSCLC): Overall survival (OS) data from the global expanded access program (EAP study-436)
- N. Maimon (Rishon Le Zion, Israel)
- N. Maimon (Rishon Le Zion, Israel)
- J. P. Stevenson (Cleveland, United States of America)
- W. Petty (Winston-Salem, United States of America)
- C. M. Ferreira (Rio de Janeiro, Brazil)
- I. Morbeck (Brasilia, Brazil)
- A. Zer (Petah Tikva, Israel)
- J. R. Bauman (Philadelphia, United States of America)
- S. Kalmadi (Chandler, United States of America)
- C. Xia (Thousand Oaks, United States of America)
- A. Meloni (Thousand Oaks, United States of America)
- T. Varrieur (Thousand Oaks, United States of America)
- M. Awad (Boston, United States of America)
Abstract
Background
Amgen study 20190436 (study-436) is a global protocol under the sotorasib EAP which allowed compassionate use of sotorasib, a first-in-class
Methods
Pts, including those with Eastern Cooperative Oncology Group performance status (ECOG PS) 2, a history of CNS metastases, additional co-morbidities, and who had exhausted other treatment options, were enrolled in 6 countries (USA, ARG, BRA, ISR, SAU, TWN) across 49 centers. The primary endpoint assessed the safety of oral sotorasib 960 mg once daily. Median OS, a key secondary endpoint, was estimated based on the time from the start of sotorasib treatment until death due to any cause.
Results
A total of 147 pts received sotorasib. At baseline, pts had received a median of 2 (range, 0–8) prior lines of anticancer therapy, 37 (25%) pts had ECOG PS 2, and 48 (33%) had a history of CNS metastases. With a median follow-up of 13.6 (95% CI, 11.1–14.6) months, the median OS was 9.5 (95% CI, 8.6–12.0) months. Among the subgroups, the median OS was numerically longer in pts with ECOG PS 0 or 1 vs ECOG PS 2; with up to 2 vs > 2 prior lines of anticancer therapies; and in pts with former vs current smoking history (
| Median OS, months (95% CI) | |
|---|---|
| All pts (N = 147) | 9.5 (8.6–12.0) |
| ECOG PS | |
| 0 or 1 (n = 110) | 10.3 (8.8–12.2) |
| 2 (n = 37) | 7.9 (6.6–NE) |
| 1 (n = 56) | 10.5 (7.9–12.5) |
| 2 (n = 47) | 11.3 (8.6–NE) |
| > 2 (n = 42) | 7.2 (5.7–12.0) |
| Never (n = 13) | 18.0 (12.2–NE) |
| Current (n = 23) | 5.8 (3.4–7.9) |
| Former (n = 111) | 10.5 (8.9–12.5) |
| Yes (n = 48) | 9.5 (6.7–12.0) |
| No (n = 99) | 10.3 (8.6–12.5) |
Data cut-off date: November 8, 2022.
Conclusions
In the first report of survival in an EAP pt population treated with sotorasib, the median OS was similar to that observed in trials. The difference in median OS was minimal in pts with or without a history of CNS metastases at baseline.
Clinical trial identification
NCT04667234.
Editorial acknowledgement
Medical writing assistance was provided by Liz Leight, an employee of Amgen Inc., and Advait A. Joshi of Cactus LifeSciences (part of Cactus Communications), which was funded by Amgen, Inc.
Legal entity responsible for the study
Amgen Inc.
Funding
Amgen Inc.
Disclosure
S. Novello: Financial Interests, Personal, Speaker's Bureau: AstraZeneca, Amgen Inc., Boehringer Ingelheim, MSD, Eli Lilly, Takeda, Pfizer, Roche, Novartis, Sanofi, GSK. J.P. Stevenson: Financial Interests, Personal, Advisory Board: BeiGene, Novartis, Medtronic, Trizell Inc; Financial Interests, Institutional, Research Grant: Merck, EMD Serono, Amgen. W. Petty: Financial Interests, Personal, Other, Consultancy role: Mirati. I. Morbeck: Financial Interests, Personal, Other, Honoraria: Astellas Pharma, Bayer, Janssen Oncology; Financial Interests, Personal, Advisory Role: AstraZeneca, BMS Brazil, Ipsen, Janssen Oncology, MSD Oncology; Financial Interests, Personal, Speaker's Bureau: MSD Oncology; Financial Interests, Personal, Research Grant: Astellas Pharma; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca. A. Zer: Financial Interests, Personal, Stocks/Shares: Nixio; Financial Interests, Personal, Other, Honoraria: AstraZeneca, Bristol Myers Squibb, MSD, Novartis, Roche, Takeda; Financial Interests, Personal, Advisory Role: Boehringer Ingelheim, Eli Lilly, MSD, Oncotest/Rhenium, Roche; Financial Interests, Institutional, Research Grant: Bristol Myers Squibb; Financial Interests, Personal, Other, Travel, Accommodations, Expenses: AstraZeneca, MSD, Roche. J.R. Bauman: Financial Interests, Personal, Advisory Board: Kura, Janssen, Pfizer, Blueprint Medicine, Eli Lilly, Merck, Mirati, Turning Point Therapeutics, BeiGene. C. Xia: Financial Interests, Personal, Full or part-time Employment: Amgen Inc.; Financial Interests, Personal, Stocks/Shares: Amgen Inc. A. Meloni: Financial Interests, Personal, Full or part-time Employment: Amgen Inc.; Financial Interests, Personal, Stocks/Shares: Amgen Inc. T. Varrieur: Financial Interests, Personal, Full or part-time Employment: Amgen Inc.; Financial Interests, Personal, Stocks/Shares: Amgen Inc. M. Awad: Financial Interests, Personal, Other, Consultancy role: Genentech, Bristol Myers Squibb, Merck, AstraZeneca, Maverick, Blueprint Medicine, Syndax, Ariad, Nektar, ArcherDX, Mirati, NextCure, Novartis, EMD Serono; Financial Interests, Institutional, Research Grant: AstraZeneca, Eli Lilly, Genentech, Bristol Myers Squibb. All other authors have declared no conflicts of interest.
8MO - Adagrasib (MRTX849) in patients with advanced/metastatic KRAS G12C-mutated non-small cell lung cancer (NSCLC): Preliminary analysis of mutation allele frequency
- P. A. Jänne (Boston, United States of America)
- P. A. Jänne (Boston, United States of America)
- A. Spira (Fairfax, United States of America)
- G. J. Riely (New York, United States of America)
- S. Gadgeel (Detroit, United States of America)
- R. Heist (Boston, United States of America)
- S. Ou (Orange, United States of America)
- M. L. Johnson (Nashville, United States of America)
- J. Sabari (New York, United States of America)
- K. Velastegui (San Diego, United States of America)
- J. G. Christensen (San Diego, United States of America)
- W. Yang (San Diego, United States of America)
- K. Anderes (San Diego, United States of America)
- R. Chao (San Diego, United States of America)
- C. Paweletz (Boston, United States of America)
Abstract
Background
KRASG12C mutations occur in ∼14% of NSCLC adenocarcinomas. Adagrasib (ada), a KRASG12C inhibitor, was selected for favorable properties, including long half-life (23 h), dose-dependent pharmacokinetics, and central nervous system penetration. In the KRYSTAL-1 registrational phase II Cohort A, ada showed clinical activity with manageable tolerability in patients (pts) with previously treated KRASG12C-mutated NSCLC.
Methods
Pts with previously treated KRASG12C-mutated NSCLC received ada 600 mg orally BID. Study objectives included objective response rate [ORR], progression-free survival [PFS], overall survival [OS], safety and exploratory correlative analyses. An exploratory analysis of clinical response for pts with detectable circulating tumor (ct) DNA at baseline, cycle 2 day 1, and cycle 4 day 1 (C4D1), who comprise the mutation allele frequency clearance (MAFC)-evaluable population, was also performed; KRASG12C ctDNA was assessed by digital droplet polymerase chain reaction.
Results
At data cutoff, 15 Oct 2021, Cohort A included 116 pts (median follow-up 12.9 months): median age 64 years, 56% female, median 2 prior systemic therapies. ORR by blinded independent central review (BICR) was 42.9%, disease control rate 79.5%, median PFS 6.5 months (95% CI 4.7–8.4) and, with longer follow-up (cutoff 15 Jan 2022), median OS 12.6 months (95% CI 9.2–19.2). Any grade treatment-related adverse events (TRAEs) occurred in 97% of pts (most commonly [>40%] diarrhea [63%], nausea [62%], vomiting [47%], and fatigue [41%]), and Grade 3–4 TRAEs in 43% (most commonly [≥5%] serum lipase increase [6%] and anemia [5%]). Two grade 5 TRAEs occurred; 8 (7%) TRAEs led to discontinuation. In MAFC-evaluable pts (n = 35), ORR by BICR was 60% (21/35) and all responses correlated with MAFC >90% by C4D1.
Conclusions
Ada showed promising efficacy and manageable tolerability in previously treated pts with KRASG12C-mutated NSCLC. Additional analyses are needed to further evaluate whether clinical response with ada correlates with MAFC in ctDNA. A phase III trial evaluating ada monotherapy vs docetaxel in previously treated pts with KRASG12C-mutated NSCLC is ongoing (NCT04685135).
Clinical trial identification
NCT03785249.
Editorial acknowledgement
KRYSTAL-1 was sponsored by Mirati Therapeutics, Inc. Third-party medical writing support, under the direction of the authors, was provided by Rebecca Benatan, BSc, of Ashfield MedComms, an Inizio company, and was funded by Mirati Therapeutics, Inc.
Legal entity responsible for the study
Mirati Therapeutics, Inc.
Funding
Mirati Therapeutics, Inc.
Disclosure
P.A. Jänne: Financial Interests, Personal, Stocks/Shares: Gatekeeper Pharmaceuticals; Financial Interests, Institutional, Funding: AstraZeneca, Boehringer Ingelheim, Eli Lilly, Revolution Medicines, Takeda Oncology, Daiichi Sankyo; Financial Interests, Personal, Advisory Role: AstraZeneca, Boehringer Ingelheim, Pfizer, Roche/Genentech, Eli Lilly, SFJ Pharmaceuticals, Voronoi, Daiichi Sankyo, Novartis, Biocartis, Takeda Oncology, Transcenta, Silicon Therapeutics, Syndax, Nuvalent, Allorion Therapeutics, Accutar Biotech, AbbVie, Bayer, Eisai, Monte Rosa, Scorpion Therapeutics, Merus, Frontier Medicines, Hongyun Biotechnology. A. Spira: Financial Interests, Personal, Invited Speaker: CytomX Therapeutics, AstraZeneca/MedImmune, Merck, Takeda, Amgen, Janssen Oncology, Novartis, Bristol-Myers Squibb, Bayer; Financial Interests, Personal, Stocks/Shares: Eli Lilly; Financial Interests, Institutional, Research Grant: LAM Therapeutics, Regeneron, Roche, AstraZeneca, Boehringer Ingelheim, Astellas Pharma, MedImmune, Novartis, Newlink Genetics, Incyte, AbbVie, Ignyta, Trovagene, Takeda, Macrogenics, CytomX Therapeutics, Astex Pharmaceuticals, Bristol-Myers Squibb, Loxo, Arch Therapeutics, Gritstone, Plexxikon, Amgen, Daiichi Sankyo, ADCT, Janssen Oncology, Mirati Therapeutics, Rubius, Synthekine, Mersana, Blueprint Medicines, Alkermes, Revolution Medicines; Financial Interests, Personal, Advisory Role: Incyte, Amgen, Novartis, Mirati Therapeutics, Gritstone Oncology, Jazz Pharmaceuticals, Takeda, Janssen Research & Development, Mersana, Gritstone Bio, Daiichi Sankyo/AstraZeneca, Regeneron, Array Biopharma, AstraZeneca/MedImmune, Merck, Bristol-Myers Squibb, Blueprint Medicines. G.J. Riely: Financial Interests, Personal, Advisory Board: Mirati Therapeutics, Novartis, Takeda, Eli Lilly, Rain Therapeutics, Merck; Financial Interests, Institutional, Research Grant: Mirati Therapeutics, Roche, Novartis, Takeda, Eli Lilly, Rain Therapeutics, Merck; Financial Interests, Personal, Principal Investigator: Mirati Therapeutics, Roche, Novartis, Takeda, Eli Lilly, Rain Therapeutics, Merck. S. Gadgeel: Financial Interests, Personal, Advisory Board: AstraZeneca, Amgen, Takeda, Genentech/Roche, Bristol Myers Squibb, Pfizer, Eli Lilly, Mirati Therapeutics, Blueprint, Daiichi Sankyo, Janssen, GSK, Merck; Financial Interests, Personal, Other, Data safety monitoring board: AstraZeneca. R. Heist: Financial Interests, Personal, Advisory Board: AbbVie, Daiichi Sankyo, Novartis, Eli Lilly, Regeneron, Sanofi, Claim, EMD Serono; Financial Interests, Institutional, Research Grant: AbbVie, Agios, Corvus, Daiichi Sankyo, Eli Lilly, Mirati Therapeutics, Novartis, Erasca, Exelixis, Turning Point. S.I. Ou: Financial Interests, Personal, Invited Speaker: Pfizer, Roche, DAVA Oncology, JNJ/Janssen; Financial Interests, Personal, Speaker's Bureau: Pfizer; Financial Interests, Personal, Advisory Board: JNJ/Janssen, Elevation Oncology; Financial Interests, Personal, Stocks/Shares: Turning Point Therapeutics, Elevation Oncology; Financial Interests, Personal, Advisory Role: Elevation Oncology. M.L. Johnson: Financial Interests, Personal, Advisory Role: AbbVie, Amgen, Astellas, AstraZeneca, Axelia Oncology, Black Diamond, Boehringer Ingelheim, Bristol Myers Squibb, Calithera, CytomX, Daiichi Sankyo, EcoR1, Editas Medicines, Eisai, EMD Serono, G1 Therapeutics, Genentech/Roche, Genmab, GSK, Gritstone Oncology, Ideaya Biosciences, iTeos, Janssen, Eli Lilly, Merck, Mirati Therapeutics, Oncorus, Regeneron, Ribon Therapeutics, Sanofi-Aventis, Turning Point Therapeutics. J. Sabari: Financial Interests, Personal, Invited Speaker: Medscape, MJHS Onclive, Clinical Care Options; Financial Interests, Personal, Advisory Role: AstraZeneca, Genentech, Janssen, Mirati Therapeutics, Pfizer, Sonfi Genzyme, Takeda. K. Velastegui: Financial Interests, Personal, Full or part-time Employment: Mirati Therapeutics; Financial Interests, Personal, Stocks/Shares: Mirati Therapeutics. J.G. Christensen: Financial Interests, Personal, Advisory Board: Bridge Biosciences; Financial Interests, Personal, Officer: Mirati Therapeutics; Financial Interests, Personal, Full or part-time Employment: Mirati Therapeutics; Financial Interests, Personal, Stocks/Shares: Mirati Therapeutics. W. Yang: Financial Interests, Personal, Full or part-time Employment: Mirati Therapeutics. K. Anderes: Financial Interests, Personal, Full or part-time Employment: Mirati Therapeutics; Financial Interests, Personal, Stocks/Shares: Mirati Therapeutics. R. Chao: Financial Interests, Personal, Full or part-time Employment: Mirati Therapeutics; Financial Interests, Personal, Stocks/Shares: Mirati Therapeutics. C. Paweletz: Financial Interests, Personal, Research Grant: Daiichi Sankyo, Bicycle Therapeutics, Transcenta, Bicara Therapeutics, AstraZeneca, Intellia Therapeutics, Janssen Pharmaceuticals, Mirati Therapeutics, Array Biopharma, Bristol Myers Squibb, Takeda Pharmaceutical Company, KSQ Therapeutics, IMPACT Therapeutics; Financial Interests, Personal, Other, Consulting: DropWorks, XSphera Biosciences; Financial Interests, Personal, Speaker's Bureau: Bio-Rad; Financial Interests, Personal, Stocks/Shares: XSphera Biosciences.
143MO - Risk of lung cancer among current smokers by pack-year smoking: A cohort study with 23 years of follow-up
- J. A. Nations (Washington, United States of America)
- J. A. Nations (Washington, United States of America)
- C. Faselis (Washington, United States of America)
- Q. Zeng-Trietler (Washington, United States of America)
- H. Sheriff (Washington, United States of America)
- S. Zhang (Washington, United States of America)
- A. Ahmed (Washington, United States of America)
Abstract
Background
We have recently demonstrated that current heavy smokers with >20 pack-year (PY) smoking history (median, 48.8, IQR, 31.6–57.0 PY) and non-heavy smokers (<20 PY; median, 11.4; IQR, 7.3–14.4 PY) have about 40- and 10-times higher risk of lung cancer, respectively (JAMA-Oncol. 2022; 8:1428–1437). In the current study, we examined the magnitude of the graded risk increase associated with PY of smoking among current smokers.
Methods
Of the 2505 community-dwelling older current smokers (mean age, 73 ± 5.7 years, 69% women, 17% African American) in the Cardiovascular Health Study (CHS), 1973 were never-smokers. The 532 current smokers were categorized based on PY smoking into: <20 (n = 95), 20–39 (n = 157), 40–59 (n = 181) and ≥60 (n = 94). Cause-specific HR (95% CI) for incident lung during 23 years of follow-up were estimated for the 4 groups (reference: never-smokers) based on Cox regression model, adjusting age, sex, race and competing risk of death.
Results
Incident lung cancer occurred in 0.5% of never smokers, and 5.0%, 14.6%, 17.7% and 16.0% of those with <20, 20–39, 40–59, and ≥60 PY smoking history, respectively. Compared with never smokers, cause-specific HRs (95% CIs) for incident lung cancer in the 4 groups with <20, 20–39, 40–59, and ≥60 PY smoking history were 9.73 (3.27–28.99), 30.33 (14.25–64.53), 42.97 (20.76–88.94), and 46.02 (20.08–105.48), respectively.
Conclusions
The risk of lung cancer among current smokers with <20 PY smoking for whom low-dose computed tomography screening is not recommended is high, but the risk was 3 and 4 times higher in those 20–39 and 40–59 PY, but plateaued for those with ≥60 PY. This study underscores the importance of smoking abstinence and early cessation.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.
Invited Discussant 7MO, 8MO and 143MO
- N. Singh (Chandigarh, India)
- N. Singh (Chandigarh, India)
9MO - Profile of immunorecognition related markers including HLA-1 expression to predict response to immunocheckpoint inhibitors in non-small cell lung cancer
- M. Saigi Morgui (Badalona, Spain)
- M. Saigi Morgui (Badalona, Spain)
- J. Mate (Badalona, Spain)
- E. Carcereny (Badalona, Spain)
- A. Esteve Gomez (Badalona, Spain)
- F. Andreo (Badalona, Spain)
- A. Martinez-Cardús (Badalona, Spain)
- M. Cucurull Salamero (Badalona, Spain)
- C. Centeno (Badalona, Spain)
- E. Pros (Badalona, Spain)
- A. López (Badalona, Spain)
- G. Cerdá (Badalona, Spain)
- M. Moran Bueno (Badalona, Spain)
- A. Hernandez Gonzalez (Badalona, Spain)
- M. Domenech Vinolas (Badalona, Spain)
- A. Muñoz-Mármol (Badalona, Spain)
- M. Sánchez-Céspedes (Badalona, Spain)
Abstract
Background
The incorporation of immunotherapy (IT) with immune-checkpoint inhibitors (ICIs) into clinical practice has represented a major breakthrough in non-small cell lung cancer (NSCLC) treatment, particularly in cases where the cancer has no druggable genetic alterations. The human histocompatibility complex (HLA-1) is essential for antigen presentation capability and immune response. Here we evaluate HLA-1 and other immune-related markers as potential predictive factors of response to ICI in NSCLC.
Methods
We evaluated the immunophenotype in a cohort of 140 metastatic NSCLC patients who received treatment with ICI based regimens for metastatic setting at ICO Badalona from 2014 to 2019. We profiled the expression levels by immunohistochemistry (IHC) of HLA-1, and other immune-related markers including CD73, CD8, and PD-L1 (Ventana SP263) from formalin-fixed paraffin-embedded (FFPE) human tissue samples. We evaluated the response and clinical outcomes to ICI. The Chi-Square test for categorical variables and Kaplan Meier method for survival analysis were performed.
Results
In our cohort of 140 patients: 86% males and 14% females, 63% were lung adenocarcinomas (LuAD) and 37% squamous cell carcinoma (SCC). They received IT treatment as a 1st line (29%), 2nd (46%), and 3rd or further lines (25%). PD-L1≥50% was present in 25% of cases. 67 patients were evaluable for HLA-1 at the moment of the analysis. Our work reveals that ∼45% of NSCLC in our cohort express low staining levels of HLA-1 (down regulation or total absence) compared to normal/high staining (55%). Those patients present worse clinical outcomes: mPFS to IT 9.1 (6.5–20.2) vs 21 (13.9-NR) months (p-value 0.028), respectively. We also report that HLA-1 is co-expressed with PD-L1 (p <0.005), regardless of histological subtype.
Conclusions
Down-regulation of HLA-1 expression is a mechanism of immune-evasion and affects a subset of NSCLC, which abrogates the response to ICI. HLA-1 IHC is an emerging immunomarker in NSCLC and predictor of response to ICI. In addition, we observed that HLA-1 is co-expressed with PD-L1 and represents a surrogate marker of immune-inflamed phenotype which might predict better outcomes to PD(L)-1 blockade.
Legal entity responsible for the study
The authors.
Funding
Merck Serono, SEOM (Sociedad Española de Oncología Médica).
Disclosure
All authors have declared no conflicts of interest.
145MO - Updated survival, efficacy and safety of adjuvant (adj) atezolizumab (atezo) after neoadjuvant (neoadj) atezo in the phase II LCMC3 study
- D. Carbone (Columbus, United States of America)
- D. Carbone (Columbus, United States of America)
- S. Waqar (Columbus, United States of America)
- J. Chaft (New York, United States of America)
- M. Kris (New York, United States of America)
- B. Johnson (Boston, United States of America)
- J. Lee (Los Angeles, United States of America)
- I. Wistuba (Houston, United States of America)
- D. J. Kwiatkowski (Boston, United States of America)
- P. A. Bunn (Aurora, United States of America)
- K. Schulze (Columbus, United States of America)
- A. Johnson (South San Francisco, United States of America)
- E. Brandao (South San Francisco, United States of America)
- M. Awad (Boston, United States of America)
- K. Reckamp (Los Angeles, United States of America)
- A. C. Chiang (New Haven, United States of America)
- A. Nicholas (South San Francisco, United States of America)
- V. W. Rusch (New York, United States of America)
- K. Brotto (San Francisco, United States of America)
Abstract
Background
Neoadj chemoimmunotherapy (IO) treatment (tx) without adj tx has shown impressive DFS outcomes but the role of adj IO after neoadj IO is unclear. LCMC3, an open-label, single-arm ph II study of neoadj atezo (anti–PD-L1) with optional adj atezo in patients (pts) with early-stage non-small cell lung cancer (NSCLC). Here we report updated DFS, OS and safety in pts who received adj atezo vs pts who did not.
Methods
Eligible pts aged ≥18 y had resectable stage IB-IIIA or select IIIB NSCLC and ECOG PS 0-1. Pts received neoadj atezo 1200 mg IV for ≤2 cycles (Days 1 and 22) followed by surgery (Day 40 ± 10). Pts without progression were offered the option to receive adj atezo every 3 weeks for ≤12 months. The primary endpoint was MPR rate (≤10% viable tumor cells at surgery) in pts without EGFR/ALK mutations. Exploratory endpoints included DFS and OS. Safety was assessed during the adj phase.
Results
Data cutoff was Oct 21, 2022. The primary efficacy population (PEP) was 137 pts without EGFR/ALK alterations who had surgery and MPR assessment. The updated 3-y DFS and OS rate for the entire group was 72% and 82%, for stage I/II was 75% and 82%, and for stage III was 68% and 81%, respectively. In the PEP, 53 pts (39%) received adj atezo and 84 (61%) did not. While not randomized, these groups were clinically well balanced. The 3-y DFS rate was 83% with adj atezo vs 64% without adj atezo (HR, 0.43; 95% CI: 0.21, 0.90; P = 0.025). In pts without MPR (n = 108) 3-y DFS for adj atezo vs without adj atezo was 80% vs 62% (HR, 0.48; 95% CI: 0.20, 1.12; P = 0.088) and 3-y OS was 87% vs 75% (HR, 0.49; 95% CI: 0.17, 1.46; P = 0.202). In the adj atezo safety population (n = 57), there were 11 treatment-related adverse events (19%; Gr 3/4, 16%) leading to discontinuation of adj atezo.
Conclusions
This exploratory analysis revealed that LCMC3 pts with resectable NSCLC who received adj atezo had improved DFS and showed a trend toward improved OS vs pts who did not receive adj atezo. Furthermore, the non-MPR subgroup had the same trend toward improved DFS and OS with adj atezo vs pts who did not receive adj atezo. Adj atezo was well tolerated, with no new safety concerns. These data suggest that adding adj IO to neoadj IO may result in improved outcomes.
Clinical trial identification
NCT02927301.
Editorial acknowledgement
Editorial assistance was provided by Michael Williams PhD of Health Interactions Inc and funded by Genentech Inc.
Legal entity responsible for the study
Genentech Inc.
Funding
Genentech Inc.
Disclosure
D.P. Carbone: Financial Interests, Personal, Other, Consultant/Independent Contractor: Iovance Biotherapies; Financial Interests, Personal, Advisory Role: Janssen, Jazz, Sanofi Genzyme, Regeneron, Glaxo-Smith Kline, Iovance Biotherapies, AbbVie; Financial Interests, Personal, Other, DMC: Lilly; Financial Interests, Personal, Other, Lung Cancer Symposium: Roche Taiwan; Financial Interests, Personal, Other, Moderator, Lung Cancer Screening Program: AstraZeneca; Financial Interests, Personal, Other, Education Program: Onc Live; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Other, Honorarium Recipient: AstraZeneca. S.N. Waqar: Financial Interests, Institutional, Invited Speaker, Institutional PI for Research study: Spectrum Pharmaceuticals, Lilly, Pfizer, Genentech/Roche, Daiichi Sankyo, Newlink Genetics, EMD Serono, Puma Biotechnology, Novartis, Xcovery, Synermore biologics, Celgene, Vertex, Bristol-Myers Squibb, Stem CentRx, Hengrui Therapeutics, Checkpoint Therapeutics, Ignyta, AstraZeneca, ARIAD, Roche, Merck; Financial Interests, Institutional, Other, This funding provides effort for Dr. Waqar to support and oversee the Lung-MAP master protocol and sub study activities: SWOG-Clinical Trials Partnership; Financial Interests, Personal and Institutional, Other, Chair of Data Safety Monitoring Board for Study: Hoosier Cancer Research Network. J. Chaft: Financial Interests, Personal, Other, Consultant: AstraZeneca, Flame Biosciences, Genentech, BMS, Merck, Guardant Health, Janssen, Novartis, Regeneron, Arcus Biosciences. M.G. Kris: Financial Interests, Personal, Other, Honoraria: AstraZeneca, BerGenBio, Pfizer, Janssen, Daiichi Sankyo, Novartis; Financial Interests, Personal, Other, Editorial support: Genentech. B.E. Johnson: Financial Interests, Personal, Full or part-time Employment, Post Marketing Royalties for EGFR mutation testing: Dana-Farber Cancer Institute; Financial Interests, Personal, Other, Independent Contractor: Novartis, Checkpoint Therapeutics, Hummingbird Diagnostics, Daiichi Sankyo, AstraZeneca, G1 Therapeutics, BlueDotBio, GSK, Hengrui Therapeutics, Simcere Pharmaceutical; Financial Interests, Personal, Other, Steering Committee member: Pfizer. J.M. Lee: Financial Interests, Personal, Advisory Board: Bristol Myers Squibb, Astrazeneca, Roche/Genentech, Novartis; Financial Interests, Personal, Invited Speaker, LCMC3, LCMC4, NAUTIKA-1: Roche/Genentech; Financial Interests, Personal, Invited Speaker, CANOPY-N, GEOMETRY-1: Novartis. I.I. Wistuba: Financial Interests, Personal, Advisory Board: Genentech/Roche, Bristol-Myers Squibb, AstraZeneca, Merck, GlaxoSimthKline, Oncocyte, Flame, Daiichi Sankyo, Amgen, Novartis, Sanofi, Jansen, Regeneron, Merus; Financial Interests, Personal, Invited Speaker: Guardant Health, MSD, Roche, Pfizer, Merck; Financial Interests, Institutional, Funding: Genentech, Medimmune/AstraZeneca, Merck, Adaptimmune, EMD Serono, Pfizer, Takeda, Amgen, Karus, Johnson & Johnson, Bayer, Iovance, 4D, Novartis, Akoya. D. Kwiatkowski: Financial Interests, Personal, Other, consultant: Guidepoint, Bridgebio, AADI; Financial Interests, Institutional, Research Grant, research grant: Genentech, AADI, Revolution Medicines. P.A. Bunn: Financial Interests, Personal, Advisory Board: Verastem, Ascentage, CStone; Financial Interests, Personal, Other, DMC Member: Merck, BMS; Financial Interests, Personal, Other, Independent Contractor: Lilly. K. Schulze: Financial Interests, Personal, Full or part-time Employment: Genentech Inc.; Financial Interests, Personal, Stocks/Shares: Roche. A.M. Johnson: Financial Interests, Institutional, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Genentech; Financial Interests, Personal and Institutional, Other, Employee of Genentech Roche – research funding for clinical trials: Genentech; Other, Personal, Other, Employee of Genentech Roche: Genentech. E. Brandao: Financial Interests, Personal, Full or part-time Employment: Genentech Inc.; Financial Interests, Personal, Stocks/Shares: Roche. M. Awad: Financial Interests, Personal, Research Grant: BMS, Lilly, Genentech, AstraZeneca, Amgen; Financial Interests, Personal, Other, Consultant: BMS, Merck, Genentech, AstraZeneca, Mirati, Blueprint Medicine, AbbVie, Gritstone, NextCure, EMD Serono. K. Reckamp: Financial Interests, Personal, Other, consultant: Amgen, AstraZeneca, Blueprint, Daiichi Sankyo, Genentech, GlaxoSmithKline, Janssen, Lilly, Mirati, Takeda; Financial Interests, Personal, Advisory Board: EMD Soreno, Merck KGA; Financial Interests, Personal, Invited Speaker: Seattle Genetics,; Financial Interests, Institutional, Invited Speaker: Genentech, Blueprint, Calithera, Daiichi Sankyo, Elevation Oncology, Janssen. A.C. Chiang: Financial Interests, Personal, Advisory Board, and consulting: AstraZeneca; Financial Interests, Personal, Advisory Board: Daichi, Genentech; Financial Interests, Institutional, Officer, SWOG Executive Officer for Lung and Breast: SWOG; Financial Interests, Institutional, Invited Speaker: AstraZeneca, AbbVie, Genentech, BMS. A. Nicholas: Financial Interests, Personal, Full or part-time Employment: Genentech; Financial Interests, Personal, Stocks/Shares: Genentech. V. Rusch: Financial Interests, Personal, Research Grant, Institutional clinical trial (Surgical PI): Genentech.
Invited Discussant 9MO and 145MO
- F. Lopez-Rios (Madrid, Spain)
- F. Lopez-Rios (Madrid, Spain)