Abstract 1279P
Background
KRAS mutations are detected in 25% of NSCLC. Data on ICI activity in these patients, particularly in each KRAS subtype are limited. The aim of this study was to collect further data in an international multi-center registry.
Methods
We conducted a retrospective multicenter study of patients receiving ICI for advanced NSCLC harboring KRAS mutations (KRAS+) and compared them with data from KRAS wild-type patients (DRIVER-) and patients with other oncogenic addictions (DRIVER+). We pooled two large databases for this study (overall 26 centers). Anonymized data were evaluated for clinic-pathological characteristics and outcomes: best response (RECIST v1.1), progression-free survival (PFS) and overall survival (OS) from ICI initiation.
Results
We included 913 patients: 421 KRAS+ patients (G12C 168, other mutations 219, missing 34) and 492 controls (191 DRIVER- and 301 DRIVER+). KRAS+ patients were predominantly male (55.1%), former/current smokers (96.1%), and median-age was 62 yr. Patients were treated by ICI (PD-1/PD-L1 inhibitors) single agent mainly in second (53.4%) or third line (25.4%). Objective response rate was 22.6%, 13.4% and 12.8% (p=0.001), median PFS was 3.2months (m), 3.5m and 2.5m (p<0.001) and median OS was 13.9m, 14.1m, 13.4m (p=0.67) in KRAS+, DRIVER- and DRIVER+ cohorts, respectively. PFS was influenced by the number of lines of treatment, PD-L1 expression, performance status and type of mutation (p<0.05). Among KRAS+ patients, ORR was 26.9% and median PFS was 4.0m in KRAS G12C vs 18.8% and 2.9m in other KRAS types. Table: 1279P
| Molecular profile | RR (%) | PFS (m.) [CI95%] | OS (from ICI initiation) (m.) [CI95%] | |
| KRAS mutation | Total | 22.6 | 3.2 [2.8-4.0] | 13.9 [10.4-16.0] |
| KRAS G12C | 26.9 | 4.0 [2.8-6.4] | 15.0 [11.2-18.6] | |
| KRAS non G12C | 18.8 | 2.9 [2.5-3.9] | 11.9 [9.4-17.8] | |
| KRAS wild-type (DRIVER-) | 13.4 | 3.5 [2.7-4.4] | 14.1 [9.6-19.5] | |
| Other driver (DRIVER+) | 12.8 | 2.5 [2.1-2.8] | 13.4 [10.0-15.6] |
Conclusions
Based on a large collaborative registry, we suggest that patients with KRAS mutations and particularly G12C derive a greater benefit from ICI monotherapy than patients with other or no alterations. These results may help optimize the therapeutic strategy for KRAS mutated patients and provide rational for future combinations.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
J. Mazieres: Honoraria (self): AstraZeneca; Honoraria (self): Roche; Honoraria (self): BMS; Honoraria (self): MSD; Honoraria (self): Takeda; Honoraria (self): Pierre Fabre; Honoraria (self): Hengrui; Honoraria (self): Daiichi. A.B. Cortot: Honoraria (self): AstraZeneca; Honoraria (self): BMS; Honoraria (self): MSD; Honoraria (self): Roche; Honoraria (self): Pfizer; Honoraria (self): Novartis; Honoraria (self): Takeda. S. Couraud: Honoraria (self): Pfizer; Honoraria (self): AstraZeneca; Honoraria (self): MSD; Honoraria (self): bms; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Lilly; Honoraria (self): Chugai. L. Greillier: Honoraria (self): MSD; Honoraria (self): BMS; Honoraria (self): AstraZeneca; Honoraria (self): Roche; Honoraria (self): AbbVie; Honoraria (self): Takeda; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Pfizer; Honoraria (self): Novartis. J.W. Neal: Honoraria (self): Research to practise; Honoraria (self): Medscape; Honoraria (self): Prime Oncology; Honoraria (self): Rockpointe; Honoraria (self): MJH CME; Honoraria (self): AstraZeneca; Honoraria (self): Exelixis; Honoraria (self): Jounce; Honoraria (self): Takeda; Honoraria (self): Lilly; Honoraria (self): Amgen. V. Gounant: Honoraria (self): AstraZeneca; Honoraria (self): Roche. A. Drilon: Honoraria (self): AbbVie; Honoraria (self): Archer; Honoraria (self): AstraZeneca; Honoraria (self): Axis; Honoraria (self): Bayer; Honoraria (self): Blueprint; Honoraria (self): Hengrui; Honoraria (self): Loxo; Honoraria (self): Roche; Honoraria (self): Pfizer; Honoraria (self): Takeda. F. Barlesi: Honoraria (self): AstraZeneca; Honoraria (self): Roche; Honoraria (self): BMS; Honoraria (self): MSD; Honoraria (self): Pfizer; Honoraria (self): Boehringer; Honoraria (self): Takeda; Honoraria (self): Lilly; Honoraria (self): Amgen. All other authors have declared no conflicts of interest.