1452P Factors associated with real-world (rw) outcomes among pts with metastatic NSCLC (mNSCLC) receiving select immuno-oncology (IO) regimens: CORRELATE
Annals of Oncology(2023)
Abstract
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). 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. 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). 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.
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Key words
metastatic nsclc,mnsclc,real-world,immuno-oncology
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