Abstract 1265P
Background
Mutations in the KRAS oncogene and STK11 and KEAP1 tumour suppressor genes are found in non-squamous NSCLC, frequently co-occur and lead to differential response to immune checkpoint inhibitors. In the randomised, phase III IMpower150 study, atezolizumab (A) + bevacizumab (B) + carboplatin/paclitaxel (CP) chemotherapy significantly prolonged PFS and OS vs BCP in patients (pts) with first-line non-squamous NSCLC. We evaluated the efficacy of A and/or B with CP in pts with and without the KRAS mutation and according to STK11/KEAP1 status in IMpower150.
Methods
1202 ITT pts were enrolled to receive ABCP, ACP or BCP. Doses were A, 1200 mg; B, 15 mg/kg; C, AUC 6 mg/mL/min and P, 200 mg/m2. Primary endpoints were OS and investigator-assessed PFS in ITT wild-type (WT; no EGFR/ALK alterations) pts (N = 1047). KRAS, STK11 and KEAP1 status were determined by ctDNA next-generation sequencing (Foundation Medicine, Inc). This post hoc analysis evaluated OS and PFS in sub-groups of pts by blood-based tumour mutational status (data cutoff: 13 Sep 2019).
Results
Among 920 mutation-evaluable ITT WT pts, 24.5% had KRAS mut, 14.5% had STK11 mut and 15.5% had KEAP1 mut tumours. Within the KRAS mut population, 44.9% of pts also had co-occurring mutations in STK11 and/or KEAP1. KRAS mut, STK11 mut and KEAP1 mut tumours were generally associated with higher tumour mutation burden levels than tumours in pts WT for these mutations. PFS and OS outcomes with ABCP, ACP and BCP in pts with and without KRAS mutation and per STK11/KEAP1 status are shown in the table. Table: 1265P
| Mutation Status | ABCP Median, months n | ACP Median, months n | BCP Median, months n | ABCP vs BCP HR 95% CI | ACP vs BCP HR 95% CI | |
| PFS | KRAS mut | 8.11 80 | 4.8 74 | 5.82 71 | 0.42 0.29, 0.61 | 0.80 0.56, 1.13 |
| KRAS WT | 8.36 235 | 6.83 234 | 7.03 226 | 0.65 0.54, 0.79 | 0.82 0.67, 0.99 | |
| KRAS mut /STK11 mut and/or KEAP1 mut | 6.03 34 | 3.2 38 | 3.35 29 | 0.49 0.28, 0.84 | 0.88 0.54, 1.46 | |
| KRAS mut /STK11 WT and KEAP1 WT | 15.21 46 | 7.39 36 | 6.9 42 | 0.36 0.22, 0.59 | 0.64 0.39, 1.05 | |
| OS | KRAS mut | 19.81 80 | 11.73 74 | 9.8 71 | 0.50 0.34, 0.72 | 0.63 0.43, 0.91 |
| KRAS WT | 18.92 235 | 19.48 234 | 18.23 226 | 0.98 0.8, 1.21 | 0.9 0.72, 1.11 | |
| KRAS mut /STK11 mut and/or KEAP1 mut | 11.1 34 | 7.93 38 | 8.67 29 | 0.6 0.34, 1.03 | 0.87 0.52, 1.45 | |
| KRAS mut /STK11 WT and KEAP1 WT | 26.18 46 | 20.96 36 | 10.68 42 | 0.43 0.26, 0.72 | 0.43 0.25, 0.74 |
Conclusions
KRAS mut pts treated with ABCP derived improvement in OS and PFS benefit compared with pts treated with BCP and showed numerical improvement vs pts treated with ACP. In KRAS mut pts, ABCP provided survival benefit regardless of STK11 and KEAP1 status. The efficacy data from this exploratory analysis suggest that ABCP could be considered a treatment option for pts with KRAS mutations, regardless of STK11 or KEAP1 status.
Clinical trial identification
NCT02366143.
Editorial acknowledgement
Medical writing assistance for this abstract was provided by Kia C. E. Walcott, PhD, of Health Interactions.
Legal entity responsible for the study
F. Hoffmann-La Roche, Ltd.
Funding
F. Hoffmann-La Roche, Ltd.
Disclosure
H. West: Honoraria (self), Advisory/Consultancy: Genentech/Roche; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: AstraZeneca. F. Cappuzzo: Advisory/Consultancy: Roche; Advisory/Consultancy: AstraZeneca; Advisory/Consultancy: Bristol-Myers Squibb; Advisory/Consultancy: Merck & Co.; Advisory/Consultancy: Takeda; Advisory/Consultancy: Pfizer; Advisory/Consultancy: Eli Lilly; Advisory/Consultancy: Bayer. M. Reck: Honoraria (self), Advisory/Consultancy: AbbVie; Honoraria (self), Advisory/Consultancy: Amgen; Honoraria (self), Advisory/Consultancy: AstraZeneca; Honoraria (self), Advisory/Consultancy: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy: Boehringer Ingelheim; Honoraria (self), Advisory/Consultancy: Eli Lilly; Honoraria (self), Advisory/Consultancy: Merck; Honoraria (self), Advisory/Consultancy: MSD; Honoraria (institution), Advisory/Consultancy: Novartis; Honoraria (self), Advisory/Consultancy: Pfizer; Honoraria (self), Advisory/Consultancy: Roche; Honoraria (self), Advisory/Consultancy: Samsung. T. Mok: Speaker Bureau/Expert testimony, Research grant/Funding (institution), Shareholder/Stockholder/Stock options, Grant, Personal Fees, Ad Board: AstraZeneca; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Grant, Personal Fees, Ad Board: Roche/Genentech; Speaker Bureau/Expert testimony, Personal Fees, Ad Board: Eli Lilly; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Grant, Personal Fees, Ad Board: Bristol-Myers Squibb; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Grant, Personal Fees, Ad Board: Boehringer Ingelheim; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Grant, Personal Fees, Ad Board: Novartis; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Grant, Personal Fees, Ad Board: Merck & Co.; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Grant, Personal Fees, Ad Board: Pfizer; Honoraria (self), Personal Fees, Ad Board: Merck Serono; Research grant/Funding (institution), Grant, Personal Fees, Ad Board: Clovis Oncology; Honoraria (self), Personal Fees, Ad Board: Vertex; Research grant/Funding (institution), Grants, Personal Fees, Ad Board: SFJ Pharmaceuticals; Advisory/Consultancy, Personal Fees, Ad Board: ACEA Biosciences; Advisory/Consultancy, Non-financial Support: geneDecode; Honoraria (self), Personal Fees, Ad Board: Oncogenex; Honoraria (self), Personal Fees, Ad Board: Celgene; Honoraria (self), Personal Fees, Ad Board: Ignyta Inc.; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Grant, Personal Fees: Taiho; Research grant/Funding (institution), Grant: Eisai; Honoraria (self), Personal Fees, Ad Board: Fishawack Facilitate Ltd; Speaker Bureau/Expert testimony, Grant, Personal Fees, Ad Board: Takeda; Honoraria (self), Personal Fees, Ad Board: Janssen; Shareholder/Stockholder/Stock options, Personal Fees, Ad Board, Other: HutchisonChiMed; Research grant/Funding (institution), Grant: XCovery; Honoraria (self), Personal Fees, Ad Board: OrigiMed; Honoraria (self), Personal Fees, Ad Board: Hengrui Therapeutics; Honoraria (self), Personal Fees, Ad Board: Sanofi-Aventis R&D; Honoraria (self), Personal Fees, Ad Board: Yuhan Corporation; Shareholder/Stockholder/Stock options, Other: Sanomics; Shareholder/Stockholder/Stock options, Other: Loxo Oncology; Honoraria (self), Speaker Bureau/Expert testimony, Personal Fees: Amoy Diagnostics Co., Ltd. R.M. Jotte: Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Speaker Bureau/Expert testimony: Roche/Genentech. M. Nishio: Speaker Bureau/Expert testimony, Research grant/Funding (institution), Grants and Personal Fees: Ono Pharmaceutical; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Grants and Personal Fees: Bristol-Myers Squibb; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Grants and Personal Fees: Pfizer; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Grants and Personal Fees: Chugai Pharmaceutical; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Grants and Personal Fees: Eli Lilly; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Grants and Personal Fees: Taiho Pharmaceutical; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Grants and Personal Fees: AstraZeneca; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Grants and Personal Fees: Boehringer Ingelheim; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Grants and Personal Fees: Merck & Co.; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Grants and Personal Fees: Novartis; Speaker Bureau/Expert testimony, Research grant/Funding (institution), Personal Fees: Sankyo Healthcare; Research grant/Funding (institution), Personal Fees: Merck Serono; Research grant/Funding (institution), Grants: Astellas. E. Kim: Shareholder/Stockholder/Stock options, Full/Part-time employment: Genentech, Inc. S. Morris: Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche. G. Shankar: Full/Part-time employment: Genentech/Roche; Shareholder/Stockholder/Stock options: Exelixis. W. Zou: Shareholder/Stockholder/Stock options, Full/Part-time employment: Roche. D. Shames: Full/Part-time employment: Genentech, Inc.; Shareholder/Stockholder/Stock options: Roche Holdings. M. McCleland: Full/Part-time employment: Genentech, Inc.; Shareholder/Stockholder/Stock options: Roche Holdings. M.A. Socinski: Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Genentech, Inc.; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): AstraZeneca; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Merck; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Guardant; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Bristol-Myers Squibb; Honoraria (self), Advisory/Consultancy, Speaker Bureau/Expert testimony: Bayer; Research grant/Funding (institution): Novartis.