Abstract 34P
Background
Nearly 1-2% of patients (pts) with non-small cell lung cancer (NSCLC) harbour RET fusions and this rare population is not well characterized.
Methods
This retrospective multi-center study included pts from 17 European centres with any stage RET+ NSCLC. Molecular profile included DNA/RNA sequencing and/or FISH analyses. Clinical, pathological, biological features and treatment outcomes (assessed by investigators) including surgery, chemotherapy (CT), immunotherapy (ICI), CT-ICI, multityrosine kinase inhibitors (MTKi) and RET inhibitors (RETi) were evaluated.
Results
In 131 pts, median (m) age was 60 years, 57% were female, 92% had adenocarcinoma (5 NOS, 1 squamous, 2 large cell neuroendocrine, 2 atypical carcinoids). 44% had smoking history, 67% were metastatic at diagnosis including 19% with brain metastases (BM). At last follow up, 30% of pts had BM. RET fusions partners were KIF5B (71%), CCDC6 (20%), others (19%). mPD-L1 expression (n=101) was 5% (0-90), mTMB (n=18) was 3.50 (0-32) mut/mB. The most frequent co-mutation was TP53 (21%). The table reports treatment outcomes. Overall survival was higher in pts treated with RETi versus no RETi (2 lines: 62 vs 17.7 months, p=0.19; >2 lines: 53.5 vs 21.2 months, p=0.0087). Progression-free survival (PFS) under RETi was 16.23 vs 7.69 months in pts with and without TP53 mutations, respectively (p=0.43). In pts treated with single agent ICI, mPD-L1 was numerically higher in responders (CR/PR/SD ≥ 6 months, n=13) than in non-responders (SD<6 months/PD, n=19) (55% vs 0%, p=0.059) and mPFS was 12.91, 7.94 and 2.18 months in pts with PR, SD and PD as best objective response, respectively. ICI was permanently stopped in 3 pts for toxicity.
Conclusions
Pts with RET+ NSCLC may have a smoking history and heterogeneous histologies. RETi treatment improves survival in pretreated pts. ICI may be effective especially in pts with high PD-L1. Table: 34P
Outcomes by treatment
| Stage | Early | Advanced | |||||
| First use of | Surgery N=31 | Double agent CT N=72 | Single agent CT N=23 | CT-ICI N=19 | ICI N=33 | MTKi N=15 | RETi N=87 |
| Median n. of line (range) | NA | 3 (2-4) | 5 (3-6) | 2 (1-2) | 4 (3-5) | 4 (3-6) | 2 (2-3) |
| ORR (N, %) | NA | 38/64 (59) | 5/18 (28) | 9/19 (47) | 10/31 (32) | 5/12 (42) | 57/77 (74) |
| mDFS/PFS (months, 95% CI) | 20 (13.4-29.3) | 8.71 (6.97-11-.8) | 2.99 (2.17-6.57) | 7.36 (3.88-NA) | 4.37 (2.76-11) | 3.88 (1.51-NA) | 17.1 (12.2-NA) |
| mDOR (months, 95% CI) | NA | 7.03 (5.13-12.5) | 3.81 (1.84-NA) | 10.6 (8.8 -NA) | 9.46 (8.74-NA) | 5.82 (1.84-NA) | 23.9 (12.3-NA) |
Legal entity responsible for the study
Institut Gustave Roussy.
Funding
Has not received any funding.
Disclosure
M. Duruisseaux: Financial Interests, Personal, Advisory Board: Astra Zeneca; Financial Interests, Personal, Advisory Board: MSD Oncology; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Janseen Oncology; Financial Interests, Personal, Advisory Board: Amgen; Financial Interests, Personal, Other, travel/accomodation: MSD; Financial Interests, Personal, Other, travel/accomodation: Boehringer Ingelheim. P. Iranzo: Financial Interests, Personal, Advisory Board, travel/accomodation: Bristol Myers Squibb Recipient; Financial Interests, Personal, Advisory Board, travel/accomodation: F. Hoffmann; Financial Interests, Personal, Advisory Board, travel/accomodation: La Roche AG; Financial Interests, Personal, Advisory Board, travel/accomodation: MSD; Financial Interests, Personal, Advisory Board, travel/accomodation: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board, travel/accomodation: MSD Oncology; Financial Interests, Personal, Advisory Board, travel/accomodation: Rovi; Financial Interests, Personal, Advisory Board, travel/accomodation: Yowa Kirin; Financial Interests, Personal, Advisory Board, travel/accomodation: Grunenthal Pharma S.A; Financial Interests, Personal, Advisory Board, travel/accomodation: Pfizer. L. Mezquita: Financial Interests, Personal, Sponsor/Funding: Amgen; Financial Interests, Personal, Sponsor/Funding: Bristol Myers Squibb; Financial Interests, Personal, Sponsor/Funding: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Roche Diagnostics; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Invited Speaker: Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Technofarma; Financial Interests, Personal, Invited Speaker: Roche; Financial Interests, Personal, Expert Testimony: Astra Zeneca; Financial Interests, Personal, Principal Investigator: Astra Zeneca; Financial Interests, Personal, Principal Investigator: Pfizer. A. Calles: Financial Interests, Personal, Advisory Board: Astra Zeneca; Financial Interests, Personal, Advisory Board: Boehringer-Ingelheim; Financial Interests, Personal, Advisory Board: Pfizer; Financial Interests, Personal, Advisory Board: Bayer; Financial Interests, Personal, Advisory Board: Roche; Financial Interests, Personal, Advisory Board: Novartis; Financial Interests, Personal, Advisory Board: Takeda; Financial Interests, Personal, Sponsor/Funding: MSD. G. Mountzios: Financial Interests, Personal, Advisory Board, travel/accomodation: Astra Zeneca; Financial Interests, Personal, Advisory Board, travel/accomodation: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board, travel/accomodation: MSD; Financial Interests, Personal, Advisory Board, travel/accomodation: Roche; Financial Interests, Personal, Principal Investigator: Novartis; Financial Interests, Personal, Principal Investigator: Astra Zeneca; Financial Interests, Personal, Principal Investigator: MSD; Financial Interests, Personal, Principal Investigator: Amgen; Financial Interests, Personal, Principal Investigator: Merck; Financial Interests, Personal, Principal Investigator: Immunomedics; Financial Interests, Personal, Principal Investigator: Sanofi; Financial Interests, Personal, Principal Investigator: GSK; Financial Interests, Personal, Principal Investigator: Bristol Myers Squibb. M. Tagliamento: Financial Interests, Personal, Other, travel/accomodation: Roche; Financial Interests, Personal, Other: Bristol Myers Squibb; Financial Interests, Personal, Other: Astra Zeneca; Financial Interests, Personal, Other: Takeda; Financial Interests, Personal, Other, medical writer: Novartis; Financial Interests, Personal, Other, medical writer: Amgen. D. Planchard: Financial Interests, Personal, Advisory Board: Astra Zeneca; Financial Interests, Personal, Advisory Board: Bristol Myers Squibb; Financial Interests, Personal, Advisory Board: Celgene; Financial Interests, Personal, Advisory Board: Daiichi Sankyo; Financial Interests, Personal, Advisory Board: Boehringer Ingelheim; Financial Interests, Personal, Advisory Board: Eli Lilly; Financial Interests, Personal, Advisory Board: Merck; Financial Interests, Personal, Advisory Board, travel/accomodation: Novartis; Financial Interests, Personal, Advisory Board, travel/accomodation: prIME Oncology; Financial Interests, Personal, Principal Investigator: Astra Zeneca; Financial Interests, Personal, Principal Investigator: Bristol Myers Squibb; Financial Interests, Personal, Proprietary Information: Eli Lilly; Financial Interests, Personal, Proprietary Information: oehringer Ingelheim; Financial Interests, Personal, Principal Investigator: Daiichi Sankyo; Financial Interests, Personal, Principal Investigator, travel/accomodation: Roche; Financial Interests, Personal, Principal Investigator, travel/accomodation: Pfizer; Financial Interests, Personal, Principal Investigator: Sanofi-Aventis; Financial Interests, Personal, Principal Investigator: Medimmun; Financial Interests, Personal, Principal Investigator: Novocure,; Financial Interests, Personal, Principal Investigator: Taiho Pharma. B. Besse: Financial Interests, Institutional, Sponsor/Funding: AbbVie, Amgen, AstraZeneca, BeiGene, Blueprint Medicines, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Cristal Therapeutics, Daiichi Sankyo, Eli Lilly, GlaxoSmithKlein (GSK), Ignyta, IPSEN, Inivata, Janssen, Merck KGaA, MSD, Nektar, Onxeo, OSE Immunotherapeutics,. M. Aldea: Non-Financial Interests, Personal, Invited Speaker, travel/accomodation: Sandoz. All other authors have declared no conflicts of interest.