Abstract & Authors:展开
Background: The most frequent genetic alteration in advanced NSCLC is KRASm in ~25% of tumors. This event associates with smoking pattern and high mutational burden, which correlate with the efficacy of CI in NSCLC. There is in silico evidence that coexisting KRASm and TP53m positively impact immuneCI benefit , but this association needs clinical validation.
Methods: We retrospectively assess the efficacy of PD-1/PDL-1 CI (atezolizumab, pembrolizumab, nivolumab or durvalumab) in a cohort of NSCLC patients whose tumors were KRASm (with or without coexisting TP53m) as assessed by a next-generation sequencing test. Endpoints were clinical benefit rate (CBR), defined as partial response or stable disease > 4 months (m), and time to progression (TTP) on immuneCI. Fisher-exact test and log-rank test P values are described.
Results: 5 pacients were identified, 68% female, median age 54 y (33-75), 95% former/current smoker; 95% adenocarcinoma; 59% with 2 or more metastatic sites; 36% immuneCI as third-line or beyond (median time from first-line to immuneCI of 7.5 m). 20 tumors had KRASm in codon 12, 3 codon 13 and 2 in codon 61. Overall, CBR was 36% (CI95% 19%-57%) and median TTP was 3.7 m (CI95% 2.2-NA). Coexisting KRASm/TP53m (n = 11) did not associate with higher CB (27% vs 50%, p = 0.56). A trend for lower TTP in the KRASm/TP53m vs TP53 wild-type was observed (2.1 vs 5.6 m, HR 0.3; p = 0.11).
Conclusions: NSCLC patients whose tumors are KRASm can have substantial benefit with immuneCI. In our series, the population with KRASm/TP53m tumors did not derive higher clinical benefit from this therapeutic intervention
Nuria Pardo Aranda