• 晚期NSCLC最常见的遗传学改变是KRASm,约占25%。与吸烟相关,高突变负荷与CI治疗疗效相关;
  • 25例患者纳入回顾性分析PD-1/PDL-1 CI治疗二代测序法确定的KRASm(伴或不伴TP53m协同突变)NSCLC患者的疗效;
  • 68%女性,中位年龄54岁,95%既往吸烟/目前正在吸烟,95%腺癌,59%具有2个或以上转移灶,36% immuneCI作为三线或以上治疗;
  • CBR为36%,中位TTP 3.7个月,11例患者存在KRASm/TP53m协同突变,与CB无关。

Outcome of KRAS mutated (m) non-small cell lung cancer (NSCLC) patients (pts) treated with immune checkpoint inhibitors (immuneCI)



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

All Authors:
Nuria Pardo Aranda