Abstract 997P
Background
STK11 and KEAP1 mutational status can impact on survival outcomes in NSCLC patients (pts) treated with immune checkpoint inhibitors (ICIs). Through a systematic review, we identified prospective trials (PTs) and cohort studies (CSs) that evaluated the efficacy of ICIs according to STK11 and KEAP1 mutational status. We conducted meta-analyses of PTs and CSs which evaluated if these mutations could impact on survival.
Methods
4 meta-analyses were conducted using PTs: (1) Overall survival (OS) of ICI-containing arms (cICI) vs. non-ICI (nICI) in STK11 mut; (2) OS of cICI vs. nICI in STK11 wt; (3) Progression-free survival (PFS) of cICI vs. nICI in KEAP1 mut; and (4) PFS of cICI vs. nICI in KEAP1 wt. In the base case, PTs assessing pembrolizumab (pembro) monotherapy (mono), pembro + chemotherapy (CT), atezolizumab (atezo) + bevacizumab (bev) + CT, durvalumab (durva) mono, and durva + tremelimumab were included. A sensitivity analysis was performed excluding atezo + bev trial from OS pooled analyses. 2 meta-analyses were conducted using 5 and 4 CSs of pts treated with cICI to compare OS and PFS of STK11 mut vs. STK11 wt, respectively. Random effects model was used.
Results
In the base case, the HR (95% CI) for OS and PFS of STK11 mut pts treated with cICI vs. nICI were 0.65 (0.50-0.83) and 0.62 (0.38-1.01), respectively. For STK11 wt, HR were 0.79 (0.62-1.01) and 0.37 (0.28-0.49). For KEAP1 mut, HR for OS and PFS were 0.80 (0.64-1.00) and 0.57 (0.39-0.84). For KEAP1 wt, HR for OS was 0.76 (0.60-0.98) and for PFS 0.37 (0.29-0.49). The exclusion of atezo trial of the OS analyses had minor impact. The meta-analyses of the CSs indicated that STK11 wt pts treated with cICI might have better outcomes: OS HR STK11 mut vs. STK11 wt: 1.98 [1.66-2.37]; PFS HR STK11 mut vs. STK11 wt: 1.70 [1.32-2.19].
Conclusions
The pooled efficacy data from clinical trials was inconclusive whether STK11 mut and KEAP1 mut pts have better survival outcomes with cICI vs. nICI. The CSs meta-analysis indicated that STK11 mut can negatively impact on survival outcomes in cICI-treated pts. The results of this study must be interpreted carefully, and trials designed to address this question are needed.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
G. de Castro Jr.: Financial Interests, Personal, Advisory Board: AstraZeneca; Financial Interests, Personal, Invited Speaker: AstraZeneca; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Invited Speaker: Bayer; Financial Interests, Personal, Advisory Board,: Bristol-Myers Squibb; Financial Interests, Personal, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Invited Speaker: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Janssen; Financial Interests, Personal, Invited Speaker: Janssen; Financial Interests, Personal, Advisory Board: Lilly; Financial Interests, Personal, Advisory Board: Merck Serono; Financial Interests, Personal, Invited Speaker: Merck Serono; Financial Interests, Personal, Advisory Board: Merck Sharp & Dohme; Financial Interests, Personal, Invited Speaker: Merck Sharp & Dohme; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Invited Speaker: Novartis; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Invited Speaker: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Advisory Board: Teva; Financial Interests, Personal, Invited Speaker: Teva; Financial Interests, Personal, Advisory Board: Yuhan; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Invited Speaker: Amgen; Financial Interests, Personal, Advisory Board: Libbs; Financial Interests, Invited Speaker: Amgen; Financial Interests, Invited Speaker: GlaxoSmithKline; Financial Interests, Invited Speaker: AstraZeneca; Financial Interests, Invited Speaker: GlaxoSmithKline; Financial Interests, Invited Speaker: Beigene; Financial Interests, Invited Speaker: Merck Sharp & Dohme; Financial Interests, Invited Speaker: Merck Sharp & Dohme; Financial Interests, Invited Speaker: Bristol-Myers Squibb; Financial Interests, Invited Speaker: Novartis; Financial Interests, Invited Speaker: Novartis; Financial Interests, Invited Speaker: Roche; Financial Interests, Invited Speaker: Bayer; Financial Interests, Invited Speaker: Merck Serono; Financial Interests, Invited Speaker: Janssen; Financial Interests, Invited Speaker: AstraZeneca. D. Kashiura: Financial Interests, Personal, Full or part-time Employment: IQVIA. G. Harada: Financial Interests, Personal, Invited Speaker: MSD. L. Lima Torres: Financial Interests, Personal, Full or part-time Employment: IQVIA. G.S. Julian: Financial Interests, Personal, Full or part-time Employment: IQVIA. All other authors have declared no conflicts of interest.