Impact of KRAS G12C mutation in patients with advanced non-squamous non-small cell lung cancer treated with first-line pembrolizumab monotherapy
Menée en France à partir de données portant sur 681 patients atteints d'un cancer du poumon non épidermoïde non à petites cellules de stade avancé, cette étude multicentique rétrospective évalue l'efficacité, du point de vue de la survie sans progression et de la survie globale, du pembrolizumab en monothérapie de première ligne selon la présence d'une mutation KRAS
Objectives : Few data are available on the impact of KRAS mutation in patients with advanced non-squamous non-small cell lung cancer (aNSCLC)treated with immunotherapy. This analysis assessed the impact of KRAS mutation on the efficiency of first-line pembrolizumab immunotherapy in aNSCLC patientswith PD-L1 ≥50%. Methods : This was a secondary analysis of the ESCKEYP study, a retrospective, national, multicenterstudy which included consecutively all metastatic NSCLC patients who initiated first-linetreatment with pembrolizumab monotherapy from May 2017 (date of pembrolizumab availabilityin this indication in France) to November 22, 2019 (pembrolizumab-chemotherapy combinationapproval). Progression-free survival (PFS) and overall survival (OS) were calculatedfrom the start of pembrolizumab treatment by the Kaplan-Meier method. Tumor responseand PFS were assessed locally. Results : Among the 681 non-squamous aNSCLC PD-L1 ≥50% patients treated with pembrolizumab in the first line, 227 (33.0%) had a KRAS mutation (KRAS G12C, 12.5%; KRAS non-G12C, 20.5%). Except among non-smokers (KRAS G12C, 0%; KRAS non-G12C, 2.9%; no KRAS mutation, 9.2%), patients presented no differences in terms of sex, age, number andsites of metastatic disease at diagnosis, use of corticosteroids, use of antibiotics,and for biological factors between wild-type KRAS, KRAS G12C and non-KRAS G12C groups. Median (95% CI) PFS in months were 7.0 (3.7-14) for KRAS G12C, 4.8 (3.4-6.7) for KRAS non-G12C and 8.5 (7.3-10.6) for wild-type KRAS genotypes (p=0.23). Median OS were 18.4 (12.6-NR), 20.6 (11.4-NR) and 27.1 (18.7-34.2)months, respectively (p=0.57). Conclusion : No difference in efficacy was observed in non-squamous aNSCLC patients treated withfirst-line pembrolizumab immunotherapy whether they presented a KRAS G12C, non KRAS G12C or wild-type KRAS genotype.
Lung Cancer 2022