Abstract 145P
Background
TETs are rare malignancies of the anterior mediastinum ranging from more indolent thymoma (T) to aggressive thymic carcinoma (TC). There is no standard treatment after platinum-based chemotherapy in refractory setting. A phase II trial reported clinical benefit for everolimus (EVE) 10mg (DCR of 88%). EVE has immune modulatory activity, of interest for patients (pts) with auto-immune disorders (AIDs), detected in up to 30% of pts. Few data exist in real-world studies.
Methods
We selected pts under EVE as a front-line or beyond for refractory TETs from a single cancer center. We analyzed epidemiologic, clinical and pathological characteristics of pts. Toxicity was evaluated according to CTCAE v4, with local evaluation of efficacy.
Results
From July 2017 to January 2022, 24 pts were included. Median (m) age at diagnosis was 47,5 (35-74), 58,3% were men, 9/24 (37,5%) showed AIDs. TC and T B2 were the most frequent subtypes (n=8, 33,3% both. EVE was used as a ≥2 line for 91% (n=22) of pts, mainly starting from standard 10 mg/daily. Toxicity is summarized in the table. 3/24 (12,5%) pts discontinued treatment due to intolerance. 5/24 (20,8%) pts required dose reduction. 1/7 (14,2%) pts achieved AID control under EVE. DCR was 62,5% (95%CI 43-81), 37.5% for TC and 75% for T (with 4 PR). The m follow-up was 51 months (mo) (95%CI 10, 65-91, 34); mTTF was 3 mo (2,21-3,78 mo). mPFS of 4 mo (95% CI 2,42-5,57 mo) and mOS of 31 mo (95% CI 20,76-41,83). mPFS was 8 mo vs 2 mo for T and TC, respectively (p=0,08). mTTF was 47 mo, 7 mo and 2 mo for pts showing PR, SD and PD respectively (p<0,001). 9 pts underwent molecular analysis, reporting P53 mutation (mut) in 2 pts, PTEN and PI3K mut in 1 pts respectively. 2 of these pts achieved prolonged disease control, 1 patient with P53 mutation with PR for 18 mo, and 1 patient with PTEN mutation with SD for 9 mo (receiving EVE as front-line). Table: 145P
Toxicity
| Treatment related AEs | All grades n (%) | Grade 3-4 n (%) |
| Weight loss | 7 (29) | 2 (8) |
| Asthenia | 6 (25) | 2 (8) |
| Mucositis | 6 (25) | 1 (4) |
| Diarrhea | 4 (16) | 1 (4) |
| Pneumonitis | 2 (8) | 2 (8) |
| Pancytopenia | 2 (8) | 2 (8) |
| Neutropenia | 1 (4) | 1 (4) |
| Hand-foot syndrome | 1 (4) | 1 (4) |
| Others | 6 (25) | 0 (0) |
Conclusions
EVE showed limited efficacy in TC. Among 16 pts with T, 25% had PR with very long duration of response. Further work to identify molecular predictors of response is needed to improve patient’s selection.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
C. Le Pechoux: Financial Interests, Personal, Advisory Board: AstraZeneca, Lilly, Nanobiotix, Amgen Julien Adam Consulting or Advisory Role: Roche, Bristol Myers Squibb, AstraZeneca, Merck Sharp & Dohme Research Funding: Sanofi (Inst), Pierre Fabre (Inst), Merck Sharp & Dohme (Inst). A. Levy: Non-Financial Interests, Personal, Other: Translational Lung Cancer Research from Sep 2019 to Sep 2021. D. Planchard: Financial Interests, Personal, Advisory Board: AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Daiichi Sankyo, Eli Lilly, Merck, Novartis, Pfizer, prIME Oncology, Peer CME, Roche; Receiving honoraria from AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Celgene, Eli Lilly. F. Barlesi: Financial Interests, Personal, Other: Genentech/Roche, Pfizer, Pierre Fabre, AstraZeneca, Bristol Myers Squibb, Boehringer Ingelheim, Lilly, Novartis, Pierre Fabre, Merck Serono, MSD Oncology, Takeda, Bayer Consulting or Advisory Role: Roche/Genentech, Pfizer, Novartis, Pierre Fabre, Bristol Myers Squibb; Financial Interests, Personal, Funding: Roche/Genentech, AstraZeneca/MedImmune, Bristol Myers Squibb, Pierre Fabre, AbbVie, Amgen, Bayer, Boehringer Ingelheim, Eisai, Lilly, Ipsen, Innate Pharma, Novartis, Merck Serono, MSD Oncology, Pfizer, Sanofi/Aventis, Takeda Patents, Royalties. B. Besse: Financial Interests, Personal, Other: 4D Pharma, AbbVie, Amgen, Aptitude Health, AstraZeneca, BeiGene, Blueprint Medicines, Boehringer Ingelheim, Celgene, Cergentis, Chugai Pharmaceutical, Cristal Therapeutics, Daiichi Sankyo, Eli Lilly, Eisai, Genzyme Corporation, GSK, Inivata, Ipsen, Janssen. All other authors have declared no conflicts of interest.