1442P - DURATION: A multicenter randomized phase II trial investigating sequential mono- (mCTX) or doublet-chemotherapy (dCTX) followed by durvalumab (D) in older or frail patients with advanced non-small cell lung cancer (NSCLC)

Background

NSCLC is a disease of the elderly, but frail and older patients (pts) are underrepresented in clinical trials with scarce data to guide treatment.

Methods

DURATION (NCT03345810) was a phase 2 trial conducted in 31 German centers between 12/17-01/22. 201 older or frail stage IV NSCLC pts (age ≥70 years and/or Charlson Comorbidity Index > 1 and/or performance status (PS) ECOG ≥ 2) were stratified to receive mCTX or dCTX according to the modified Cancer Aging Research Group score (mCARG >3 or <3, respectively), and subsequently randomized between 4 cycles of CTX and 2 cycles of CTX followed by D. Primary endpoint was the rate of treatment-related grade III/IV adverse events (AEs).

Results

The median follow-up was 36.8 months (mo) with 17% of pts censored. Median age was 76 years (range 56-90), 59 pts (30%) had an ECOG PS ≥2 and 112 pts (56%) a CCI >1. The PD-L1 tumor proportion score was 0%, 1-49% and >50% in 42%, 50% and 8% of pts, respectively. The rate of grade III/IV AEs was 34%, 34%, 24% and 29% for dCTX , dCTX-D, mCTX-D and mCTX respectively (p=0.68). Treatment-related deaths were reported in 1% (n=2, dCTX-D and mCTX). 2nd-line treatment (proportion anti-PD-1/PD-L1) was administered in 57% (43%), 42% (12%), 31% (16%), 38% (22%) cases after dCTX, dCTX-D, mCTX-D and mCTX, respectively. In the modified per-protocol (PP) population (including pts treated until cycle 3, excluding pts with major protocol deviations), the median overall survival (OS) was 14.3 vs 11.1 mo for dCTX and dCTX-D (HR 1.2, p=0.46) and 10.2 vs 8.3 mo for mCTX-D and mCTX (HR 0.7, p=0.25). Pts with mCARG ≤3 had significantly longer OS compared to patients with mCARG >3 in the PP population (11.0 mo vs. 5.3 mo in median, HR 2.10, p<0.001).

Conclusions

The mCARG score stratified older or frail pts with advanced NSCLC for safe treatment conductance on dCTX, resulting in longer OS without increased toxicity compared to mCTX. The rate of grade III/IV-AEs did not exceed 34% and treatment-related mortality was ≤ 1% in both strata. Immature data show a numerical OS advantage for mCTX-D compared to mCTX, which may be related to the low rate of 2nd-line treatment < 40% in these most frail cases.

Clinical trial identification

NCT03345810.

Editorial acknowledgement

Legal entity responsible for the study

AIO Study group DKG.

Funding

AstraZeneca, BMS.

Disclosure

J.B. Kuon: Non-Financial Interests, Personal, Research Funding: AstraZeneca, BMS. A. Stenzinger: Other, Personal, Advisory Board: Aignostics, Amgen, AstraZeneca, Bayer, BMS, Ilumina, Incyte, Janssen, MSD, Novartis. P. Christopoulos: Financial Interests, Personal, Advisory Board: AstraZeneca, Boehringer Ingelheim, Chugai, Pfizer, Novartis, MSD, Takeda, Roche, Daiichi Sankyo; Financial Interests, Personal, Writing Engagement: Gilead; Financial Interests, Personal, Invited Speaker: Thermo Fisher; Financial Interests, Institutional, Funding: AstraZeneca, Boehringer Ingelheim, Amgen, Novartis, Roche; Financial Interests, Personal, Funding: Takeda. All other authors have declared no conflicts of interest.