Abstract 1452P
Background
PD-(L)1 inhibitors ± chemotherapy (CTx) have demonstrated significant survival benefit vs CTx in randomised controlled trials (RCTs) in mNSCLC. However, subgroups that may benefit less from current standard of care regimens have emerged, such as those with mutations (m) in STK11, KEAP1 and KRAS. One aim of CORRELATE was to determine factors associated with OS and rwPFS in pts receiving 1L IO treatment (tx).
Methods
This analysis included pts from the US Flatiron Clinico-Genomic Database who had mNSCLC (progressed or de novo), started 1L IO tx between 1 Nov 2016 and 31 May 2021, and met eligibility criteria based on 4 RCTs for tx with a US approval in mNSCLC (KEYNOTE [KN]-024 [n=95], KN-189 [n=462], KN-407 [n=122] and IMpower150 [n=4]). Association of pt characteristics and select 2-way interactions with OS and rwPFS were explored. Those variables that were statistically significant (p<0.05) were included in multivariate Cox regression models along with STK11, KEAP1, KRAS and PD-L1 status.
Results
Of 683 pts, 65% were aged ≥65 y, 88% white and 54% male. 21% had PD-L1 ≥50% and 34% had PD-L1 ≥1% (53% unknown PD-L1); 80% had ECOG performance status (PS) 0/1 and 90% were former/current smokers. 15%, 13% and 31% had STK11m, KEAP1m and KRASm tumours, respectively. Median OS was 15.2 mo (95% CI 13.5–17.6); median rwPFS was 6.0 mo (5.6–6.8). Multivariate Cox regression showed male sex (p=0.021), lower PD-L1 expression (p=0.030), higher PS (p<0.0001) and multiple baseline mets (p<0.0001) were associated with higher risk of death; and lower PD-L1 expression (p=0.049), higher PS (p<0.0001) and multiple baseline mets (p<0.0001), with higher risk of progression/death. Pts with STK11m had a higher risk of death (HR 1.52 [95% CI 1.17–1.97]; p=0.002) and progression/death (1.54 [1.22–1.94]; p<0.0001). Pts with KRASm had an increased risk of death vs KRAS wild-type; this effect was greater among non-smokers (HR 2.66 [1.33–5.35]); p=0.006).
Conclusions
In pts with mNSCLC receiving 1L IO tx at primarily community US practices, STK11m was associated with worse OS and rwPFS. Smoking history modified the effect of KRASm on OS. These hard-to-treat populations may require novel combination tx approaches to overcome resistance.
Clinical trial identification
Editorial acknowledgement
Medical writing support for the development of this abstract was provided by Samantha Holmes, DPhil, of Ashfield MedComms (Macclesfield, UK), an Inizio company, and was funded by AstraZeneca.
Legal entity responsible for the study
AstraZeneca PLC.
Funding
AstraZeneca.
Disclosure
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; Financial Interests, Institutional, Research Grant: Alkermes, Elevation Oncology, Genentech, Gilead, Merck, Merus, Nuvalent, Rapt, Turning Point Therapeutics. R.J. Salomonsen: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca; Financial Interests, Personal, Project Lead: 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: AstraZeneca. L. Cai: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. J. Schmidt: Financial Interests, Personal, Full or part-time Employment: AstraZeneca. S. Sadow: Financial Interests, Personal, Full or part-time Employment: AstraZeneca; Financial Interests, Personal, Stocks/Shares: AstraZeneca. 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 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, Foundation Med; 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; Financial Interests, Personal, Member: ESMO, ASCO, AACR, IASLC, SSOM, SAKK, ETOP; Financial Interests, Personal, Advisory Board: Cf. advisory boards; Financial Interests, Personal, Leadership Role: Vice President Swiss Cancer League, past President ESMO, Strategic Advisory board SPCC (Paris Saclay) Chair, ETOP scientific chair.
Resources from the same session
1379P - Preliminary results of phase II KUNPENG study of vebreltinib in patients (Pts) with advanced NSCLC harboring c-MET alterations
Presenter: Jin-Ji Yang
Session: Poster session 20
1380P - Treatment (Tx) sequencing with tepotinib in previously treated patients (pts) with MET exon 14 (METex14) skipping NSCLC in the VISION trial
Presenter: Santiago Viteri
Session: Poster session 20
1381P - TOGETHER: Pooled real-world datasets of METex14 skipping NSCLC and adjusted comparison of upfront (chemo-)immunotherapy with tepotinib from VISION
Presenter: Petros Christopoulos
Session: Poster session 20
1382P - Liquid biopsies (LBx) and tissue biopsies (TBx) for identifying MET exon 14 (METex14) skipping in advanced NSCLC: Analyses from the phase II VISION study of tepotinib
Presenter: Christian Rolfo
Session: Poster session 20
1383P - Efficacy of capmatinib compared to standard of care for German patients with locally advanced or metastatic NSCLC harboring METex14 mutations: Results from the RECAP study
Presenter: Anna Kron
Session: Poster session 20
1384P - Phase II study of cabozantinib in patients with MET-altered lung cancers
Presenter: Guilherme Harada
Session: Poster session 20
1385P - Genomics of early progression on selpercatinib in patients with RET fusion-positive lung cancers
Presenter: Monica Chen
Session: Poster session 20
1386P - Validation of MET amplification using next-generation sequencing in lung adenocarcinoma
Presenter: Marta Salido
Session: Poster session 20
1387P - Efficacy of first-line treatment options in advanced HER2-altered non-small cell lung cancer: A multi-center retrospective study
Presenter: haifeng sun
Session: Poster session 20
1388P - Real-world prognostic value of RET fusions in advanced non-small cell lung cancer (aNSCLC)
Presenter: Shirish Gadgeel
Session: Poster session 20