1172MO - Durvalumab consolidation in patients with stage III non-resecable NSCLC with driver genomic alterations

Background

Durvalumab is the standard-of-care as consolidation therapy after chemo-radiation (ChRT) in stage III non-resecable non-small cell lung cancer (NSCLC). Its activity across NSCLC patients (pts) with genomic alterations (GA) is poorly characterized. We aimed to assess durvalumab outcomes in the context of oncogenic addition.

Methods

Retrospective study of pts with stage III non-resecable NSCLC treated with durvalumab after ChRT between Apr/15 and Oct/20 at 25 centres from Europe and United States. Clinical and biological data were collected; driver GA (dGA) included EGFR/all-BRAF/all-KRAS mutations (m) and ALK/ROS1 rearrangements (r). Radiological response was assessed according to RECIST v1.1 or investigator’s criteria. We evaluated progression-free survival (PFS) and overall survival (OS) based on dGA.

Results

Out of 323 pts included, 43 had one dGA: KRASm (26; n=8 G12C), EGFRm (8; n=6 del19/ex21), BRAFm (5; n=4 V600E) and ALKr (4). Median age was 66 [39-84], gender ratio 1:1, with 98% PS ≤1 and 19% non-smokers; 88% had adenocarcinoma. PD-L1 was positive in 85% (n=4 missing). Median PFS was 17.5 months (mo.) (95%CI, 13.2-24.9) and mOS 47 mo. (95%CI, 47-not reached [NR]). No statistically significant differences in terms of mPFS were observed between dGA vs. non-dGA pts: 14.9 mo. (95%CI, 8.1-NR) vs. 18 mo. (95%CI, 13.4-28.3) (P=1.0); mOS was immature. Median PFS and OS rate at 18 mo. by each dGA are detailed in the table. Table: 1172MO

Within dGA pts, neither OS nor PFS were correlated with PD-L1 expression, whereas PFS was positively associated with smoking status: 19.2 mo. (95%CI, 11.3-NR) vs. 5.8 mo. (95%CI, 3.9-NR) in non-smokers (P=0.001).

Conclusions

We observed limited activity of durvalumab consolidation in pts with stage III non-resecable NSCLC with dGA, except for those harbouring KRASm. Larger studies are needed to confirm these findings.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

E. Auclin: Financial Interests, Institutional, Other: Mundipharma; Financial Interests, Personal and Institutional, Other: Sanofi Genzymes. R. Lopez Castro: Financial Interests, Institutional, Sponsor/Funding, Advisory role, lectures, other: Roche; Financial Interests, Institutional, Sponsor/Funding: Boehringer Ingelheim; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria, Clinical Research: Bristol Myers Squibb; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria, Clinical Research: AstraZeneca; Financial Interests, Institutional, Advisory Role, Other: Novartis. J. Bosch Barrera: Financial Interests, Personal and Institutional, Research Grant: Roche; Financial Interests, Personal and Institutional, Research Grant: Pfizer; Financial Interests, Personal and Institutional, Other: MSD; Financial Interests, Personal and Institutional, Other: BMS; Financial Interests, Personal and Institutional, Other: AstraZeneca; Financial Interests, Personal and Institutional, Other: Novartis; Financial Interests, Personal and Institutional, Other: Pierre Fabre; Financial Interests, Personal and Institutional, Other: Boehringer Ingelheim. S. Pilotto: Financial Interests, Institutional, Funding, Lectures: Roche; Financial Interests, Institutional, Funding, Lectures: Pfizer; Financial Interests, Institutional, Funding, Lectures: Merck Serono; Financial Interests, Institutional, Funding, Lectures: BMS; Financial Interests, Institutional, Invited Speaker: MSD; Financial Interests, Institutional, Invited Speaker: Lilly; Financial Interests, Institutional, Invited Speaker: Amgen; Financial Interests, Institutional, Invited Speaker: Boehringer Ingelheim; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Takeda. M. Tagliamento: Financial Interests, Institutional, Other: Roche; Financial Interests, Institutional, Other: Bristol Myers Squibb; Financial Interests, Institutional, Other: AstraZeneca; Financial Interests, Other: Takeda; Financial Interests, Writing Engagements: Novartis; Financial Interests, Writing Engagements: Amgen. E. Nadal: Financial Interests, Funding, Lectures: Roche; Financial Interests, Funding: Pfizer; Financial Interests, Funding, Lectures: Merck Serono; Financial Interests, Funding, Lectures: BMS; Financial Interests, Advisory Board: MSD; Financial Interests, Advisory Board: Lilly; Financial Interests, Advisory Board: Amgen; Financial Interests, Advisory Board: Boehringer Ingelheim; Financial Interests, Advisory Board: AstraZeneca; Financial Interests, Advisory Board: Takeda. D. Signorelli: Financial Interests, Institutional, Advisory Role: AstraZeneca; Financial Interests, Institutional, Advisory Role: Boehringer Ingelheim; Financial Interests, Institutional, Advisory Role, Other: Merck Sharp & Dohme; Financial Interests, Institutional, Other: Roche; Financial Interests, Institutional, Other: Bristol Myers Squibb. B. Besse: Financial Interests, Institutional, Sponsor/Funding: AbbVie; Financial Interests, Institutional, Sponsor/Funding: Amgen; Financial Interests, Institutional, Sponsor/Funding: AstraZeneca; Financial Interests, Institutional, Sponsor/Funding: BioGene; Financial Interests, Institutional, Sponsor/Funding: Blueprint Medicines; Financial Interests, Institutional, Sponsor/Funding: BMS; Financial Interests, Institutional, Sponsor/Funding: Boehringer Ingelheim; Financial Interests, Institutional, Sponsor/Funding: Celgene; Financial Interests, Institutional, Sponsor/Funding: Cristal Therapeutics; Financial Interests, Institutional, Sponsor/Funding: Daiichi Sankyo; Financial Interests, Institutional, Sponsor/Funding: Eli Lilly; Financial Interests, Institutional, Sponsor/Funding: GSK; Financial Interests, Institutional, Sponsor/Funding: Ignyta; Financial Interests, Institutional, Sponsor/Funding: Ipsen; Financial Interests, Institutional, Sponsor/Funding: Inivata; Financial Interests, Institutional, Sponsor/Funding: Janssen; Financial Interests, Institutional, Sponsor/Funding: Merck KGaA; Financial Interests, Institutional, Sponsor/Funding: MSD; Financial Interests, Institutional, Sponsor/Funding: Nektar; Financial Interests, Institutional, Sponsor/Funding: Onxeo; Financial Interests, Institutional, Sponsor/Funding: OSE Immunotherapeutics; Financial Interests, Institutional, Sponsor/Funding: Pfizer; Financial Interests, Institutional, Sponsor/Funding: PharmaMar; Financial Interests, Institutional, Sponsor/Funding: Roche-Genentech; Financial Interests, Institutional, Sponsor/Funding: Sanofi; Financial Interests, Institutional, Sponsor/Funding: Servier; Financial Interests, Institutional, Sponsor/Funding: Spectrum Pharmaceuticals; Financial Interests, Institutional, Sponsor/Funding: Takeda; Financial Interests, Institutional, Sponsor/Funding: Tiziana Pharma; Financial Interests, Institutional, Sponsor/Funding: Tolero Pharmaceuticals. D. Planchard: Financial Interests, Institutional, Advisory Role, Lectures, Clinical Research, Honoraria, other: AstraZeneca; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria, Clinical Research: Bristol Myers Squibb; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria, Clinical Research: Boehringer Ingelheim; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria, Clinical Research: Celgene; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria, Clinical Research: Daiichi Sankyo; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria, Clinical Research: Eli Lilly; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria, Clinical Research, Other: Merck; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria, Clinical Research, Other: Novartis; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria, Clinical Research, Other: Pfizer; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria, Other: prIME Oncology; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria: Peer CME; Financial Interests, Institutional, Advisory Role, Lectures, Honoraria, Clinical Research, Other: Roche; Financial Interests, Institutional, Principal Investigator: MedImmune; Financial Interests, Institutional, Principal Investigator: Sanofi-Aventis; Financial Interests, Institutional, Principal Investigator: Taiho Pharma; Financial Interests, Institutional, Principal Investigator: Novocure. L. Mezquita: Financial Interests, Institutional, Advisory Role: Roche; Financial Interests, Institutional, Invited Speaker: Bristol Myers Squibb; Financial Interests, Institutional, Invited Speaker: Tecnofarma; Financial Interests, Institutional, Invited Speaker: AstraZeneca; Financial Interests, Institutional, Invited Speaker: Chugai. All other authors have declared no conflicts of interest.