68P - Real-world (rw) outcomes in patients (pts) with metastatic (m) NSCLC and STK11, KEAP1 and/or KRAS mutations (mut) receiving PD-(L)1-based treatment (tx): CORRELATE

Background

PD-(L)1 inhibitors ± chemotherapy (CT) have demonstrated survival benefit vs CT in mNSCLC RCTs. However, STK11mut and KEAP1mut tumours have been characterised as immunologically ‘cold’ and are frequently associated with a concomitant KRASmut. One aim of CORRELATE was to describe rw outcomes of pts with mNSCLC and STK11, KEAP1 and/or KRAS mut receiving tx with anti-PD-(L)1 ± CT.

Methods

This analysis included pts from the US Flatiron Clinico-Genomic Database who started 1L anti-PD-(L)1 tx for mNSCLC between 1 Nov 2016 and 31 May 2021, and met eligibility criteria based on 4 RCTs for US-approved tx (KEYNOTE [KN]-024, n=94; KN-189, n=462; KN-407, n=122; IMpower150, n=4). OS and rwPFS were estimated in subgroups based on STK11, KEAP1 and KRAS mut status by Kaplan-Meier analysis. Unadjusted HRs were calculated by univariate Cox regression and adjusted HRs by multivariable Cox regression.

Results

Of 682 pts, 44% had ≥1 mut of interest. Among pts with ≥1 mut, there were more smokers, pts with ECOG PS 2 or ≥3, and pts with non-squamous tumours vs pts with no mut (each nominal p<0.05). There was a trend towards increased risk of death in pts with 1 mut vs no mut; pts with co-mut (≥2 mut) had almost 2x increased risk of death vs no mut, both with and without adjustment for pt characteristics (Table). Pts with STK11mut and pts with KRASmut (± co-mut) had a 46% and 28% increased risk of death vs STK11wt and KRASwt, respectively, after adjustment (Table). After adjusting for potential confounders, the 26% increased risk of death among pts with KEAP1mut vs KEAP1wt was not statistically significant. Trends were similar for rwPFS. Table: 68P

^a± co-mut. ^bvs no mut. ^cvs wt. ^dAdjusted for age, sex, smoking status, ECOG PS, histology, PD-L1 status, no. of baseline metastases; also adjusted for: ^eKEAP1 & KRAS status, ^fSTK11 & KRAS status, ^gSTK11 & KEAP1 status

Conclusions

In US pts with mNSCLC receiving 1L anti-PD-(L)1 ± CT, those with mut in STK11, KEAP1, KRAS, and particularly co-mut, had worse OS and rwPFS. These results highlight the need for novel combination tx approaches in these pts that might further boost immune responses (e.g., incorporating anti-CTLA-4) and optimise outcomes.

Editorial acknowledgement

Medical writing support for the development of this abstract, under the direction of the authors, was provided by Samantha Holmes, DPhil, of Ashfield MedComms (Macclesfield, UK), an Inizio company.

Legal entity responsible for the study

AstraZeneca PLC.

Funding

AstraZeneca.

Disclosure

S. Peters: Financial Interests, Institutional, Invited Speaker: AiCME, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, ecancer, Eli Lilly, Foundation Medicine, GSK, Illumina, Imedex, Ipsen, Medscape, Merck Sharp and Dohme, Mirati, Novartis, PER, Peerview, Pfizer, Roche/Genentech, RTP, Sanofi, Takeda; Financial Interests, Institutional, Advisory Board, Consultation/Advisory role: AbbVie, AiCME, Amgen, Arcus, AstraZeneca, Bayer, BeiGene, BerGenBio, Biocartis, BioInvent, Blueprint Medicines, Boehringer Ingelheim, Bristol Myers Squibb, Clovis, Daiichi Sankyo, Debiopharm, ecancer, Eli Lilly, Elsevier, F-Star, Fishawack; Financial Interests, Institutional, Member of Board of Directors: Galenica; Financial Interests, Institutional, Principal Investigator: Amgen, Arcus, AstraZeneca, BeiGene, Bristol Myers Squibb, GSK, iTeos, Merck Sharp and Dohme, Mirati, Pharma Mar, Promontory Therapeutics, Roche/Genentech, Seattle Genetics; Non-Financial Interests, Personal, Member: ESMO, ASCO, AACR, IASLC, SSOM, SAKK, ETOP; Non-Financial Interests, Personal, Advisory Role: Cf. advisory boards; Non-Financial Interests, Personal, Leadership Role: Vice President Swiss Cancer League, past President ESMO, Strategic Advisory board SPCC (Paris Saclay) Chair, ETOP Scientific Chair; Financial Interests, Institutional, Advisory Board: Foundation Medicine, Genzyme, Gilead, GSK, Hutchmed, Illumina, Imedex, IQVIA, Incyte, Ipsen, iTeos, Janssen, Medscape, Medtoday, Merck Sharp and Dohme, Merck Serono, Merrimack, Mirati, Novartis, Novocure, OncologyEducation, Pharma Mar, Promontory Therapeutics, PER, Peerview, Pfizer, Regeneron, RMEI, Roche/Genentech, RTP, Sanofi, Seattle Genetics, Takeda, Vaccibody. R.J. Salomonsen: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca; Non-Financial Interests, Personal, Project Lead: AstraZeneca. F. Skoulidis: Financial Interests, Personal, Invited Speaker: ESMO, Japanese Lung Cancer Society, Medscape Llc, Intellisphere Llc, VSPO McGill Universite de Montreal, RV Mais Promocao Events LTDS, MJH Life Sciences, IDEOlogy Health, MI&T, PER Llc, CURIO Llc, DAVA Oncology, American Association for Cancer Research, IASLC; Financial Interests, Personal, Advisory Board: AstraZeneca, Amgen Inc, Revolution Medicines, Novartis, BridgeBio, BeiGene, BergenBio, Guardant Health, Tango Therapeutics, Calithera Bioscieces, Hookipa Pharma, Novocure, Merck & Co; Financial Interests, Personal, Stocks/Shares: BioNTech SE, Moderna Inc; Financial Interests, Institutional, Research Grant: Revolution Medicines, Mirati Therapeutics, Amgen Inc, Novartis, Merck & Co; Financial Interests, Personal, Principal Investigator: Amgen Inc, AstraZeneca, Revolution Medicines, Novartis, Merck & Co, Tango Therapeutics, Genentech/Roche; Financial Interests, Personal, Advisory Role: AstraZeneca. I. Diaz Perez: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. A. Wang: Financial Interests, Personal, Full or part-time Employment, Contracted to AstraZeneca: AstraZeneca. M. Cooper: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. S.V. Liu: Financial Interests, Personal, Advisory Board: AbbVie, Amgen, AstraZeneca, Boehringer Ingelheim, Bristol Myers Squibb, Catalyst, Daiichi Sankyo, Eisai, Elevation Oncology, Genentech/Roche, Gilead, Guardant Health, Janssen, Jazz Pharmaceuticals, Merck, Merus, Mirati, Novartis, Regeneron, Sanofi, Takeda, Turning Point Therapeutics; Financial Interests, Institutional, Research Grant: AbbVie, Alkermes, Elevation Oncology, Ellipses, Genentech, Gilead, Merck, Merus, Nuvalent, RAPT, Turning Point Therapeutics.