Abstract 1294P
Background
In EGFR mutated, metastatic (met) NSCLC, outcomes from EGFR tyrosine kinase inhibitors (TKIs) have differed historically by mutation (mut) type present, with lower benefit reported in pts with an exon 21 L858R (ex21) versus (v) an exon 19 deletion (ex19). In the phase 3 RELAY trial, RAM+ERL provided a superior PFS v PBO+ERL (Nakagawa K, et al, Lancet Oncol. 2019.20:1655-69). Additional efficacy and safety by mut type are reported here for the first time.
Methods
Pts with untreated met NSCLC, an EGFR ex19 or ex21 mut, and no CNS mets were randomized (1:1) to receive erlotinib (150 mg/day) with either ramucirumab (10 mg/kg) (RAM+ERL) or placebo (PBO+ERL), Q2W, until RECIST1.1-defined progression or unacceptable toxicity. Stratification factors included mut type (ex19/ex21) and region (East Asia/Other). The primary endpoint was PFS. Secondary and exploratory endpoints included ORR, DCR, DOR, safety, PFS2, and biomarker analyses. Statistical analyses included Cox regression and Kaplan-Meier estimation. Adverse events were evaluated using NCI-CTCAE 4.0.
Results
More pts with ex21 v ex19 (83% v 72%) were of Asian race. PFS, ORR, and DCR showed consistent improvements across mut types for RAM+ERL v PBO+ERL (Table). The safety profile (Grade ≥3, serious AEs, dose adjustments) was similar between the mut types. Exploratory data are forthcoming. Table: 1294P
| Ex19 | Ex21 | |||
| RAM+ERL (n=123) | PBO+ERL (n=120) | RAM+ERL (n=99) | PBO+ERL (n=105) | |
| PFS | ||||
| Median, months | 19.6 | 12.5 | 19.4 | 11.2 |
| HR* (95% CI)*; Log-rank p-value* | 0.651 (0.469-0.903); p=0.01 | 0.618 (0.437-0.874); p=0.006 | ||
| 1yr PFS rate, % | 74 | 54 | 70 | 47 |
| ORR, % | 79 | 83 | 74 | 66 |
| DCR, % | 96 | 96 | 95 | 95 |
| DOR n responders | 97 | 99 | 73 | 69 |
| Median, months | 18.2 | 11.0 | 16.2 | 11.1 |
| HR (95% CI)* | 0.542 (0.380-0.772) | 0.731 (0.493-1.083) |
PFS, progression free survival; ORR, objective response rate; DCR, disease control rate; DOR, duration of response; HR, hazard ratio Median follow-up time = 20.7 mo (range, 0.1-35.4) *unstratified.
Conclusions
RAM+ERL-treated pts with ex21 mut had similar treatment benefit as pts with ex19 mut, which was consistent with that of the ITT. The safety profiles were as expected. These results support RAM+ERL as a first-line therapy for both ex19 and ex21-positive met NSCLC.
Clinical trial identification
NCT02411448.
Editorial acknowledgement
Susan P. Whitman, PhD, a full-time employee of Eli Lilly and Company, provided medical writing and editing support for this work.
Legal entity responsible for the study
Eli Lilly and Company.
Funding
Eli Lilly and Company.
Disclosure
K. Nakagawa: Honoraria (institution), Research grant/Funding (institution): MSD KK, Eli Lilly Japan, BMS, Taiho Pharma; Honoraria (institution), Research grant/Funding (institution): Ono Pharmaceutical, Chugai Pharma, AZ KK, Astellas Pharma; Research grant/Funding (institution): Merck Serono, IconJapan, Parexel international, IQVIA Services, A2 Healthcare, AbbVie; Honoraria (institution), Research grant/Funding (institution): Novartis Pharma KK, Nipon BI, Pfizer Japan, ; Honoraria (institution), Research grant/Funding (institution): Takeda,Symllio Pharmaceuticals, Daiichi Sanyo; Honoraria (institution), Research grant/Funding (institution): Linical Co, Otsuka Pharma, EPSInternational; Honoraria (self), Honoraria (institution): Quintiles, CMIC Shift Zero KK, Eisai Co, Kissei Pharma, Kyowa HakkoKirin, EPS Corp, Bayer Yakuhin, ; Honoraria (self), Honoraria (institution): Inventiv Health Japan, Gritsone Oncology, GlaxoSmithKline KK, Yakult Honsha, Covance; Honoraria (self), Honoraria (institution): Kyorin, CArenet, Nichi-Iko, Hisamitsu,Yodosha, ClinicalTrial Co, Medicus Shuppan, Ayumi Pharmaceutical, Nikkei business publications, ; Honoraria (self), Honoraria (institution): Thermo Fisher KK, Nanzando, Medical Review Co, Yomiuri Telecasting Corp, Reno Medical KK. E. Nadal: Travel/Accommodation/Expenses: Eli Lilly; Advisory/Consultancy: Lilly, Roche, AZ, BI. E.B. Garon: Research grant/Funding (institution): AZ, BMS, Eli Lilly, Genentech, Merck, Novartis, Iovance, Neon, Dynavax Mirati; Honoraria (self), Honoraria (institution): Dracen, EMD Serono. M. Nishio: Honoraria (institution), Research grant/Funding (institution): Eli Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony, Research grant/Funding (institution): Ono, BMS. T. Seto: Research grant/Funding (institution): Eli Lilly; Honoraria (self), Honoraria (institution), Research grant/Funding (institution): Astellas, AZ, Chugai. N. Yamamoto: Honoraria (self), Honoraria (institution): Eli Lilly, Chugai, Pfizer, ONO,AZ, ; Research grant/Funding (institution): Lilly, Chugai, Quintiles, Pfizer, Astellas,Daiichyo Sankyo, Esai, Novartis, Kyowa-Hakko Kirin,Taiho, BI. K. Park: Advisory/Consultancy: Amgen, Astellas, Bluprint, BI,Eli Lilly,GSK Hanmi, KHK,MSD, BMS,ONO, Roche, Merck KGaA, Loxo; Advisory/Consultancy, Research grant/Funding (institution): AZ. J-Y. Shih: Advisory/Consultancy, Speaker Bureau/Expert testimony: AZ, Novartis, ONO, AbbVie; Speaker Bureau/Expert testimony: ELi Lilly; Advisory/Consultancy, Speaker Bureau/Expert testimony, Travel/Accommodation/Expenses: Roche, BI, Pfizer, MSD,BMS; Advisory/Consultancy: AbbVie. B. Frimodt-Moller: Shareholder/Stockholder/Stock options, Full/Part-time employment: Eli Lilly. A.H. Zimmermann: Shareholder/Stockholder/Stock options, Full/Part-time employment: Eli Lilly. C.M. Visseren-Grul: Shareholder/Stockholder/Stock options, Full/Part-time employment: Eli Lilly. M. Reck: Honoraria (institution), Advisory/Consultancy: AbbVie, Amgen, AZ,BMS, BI; Honoraria (institution), Advisory/Consultancy: Celgene, Merck, MSD, Novartis,Pfizer, Roche.