538P - First-line chemoimmunotherapy for metastatic thymic carcinoma

Background

Thymic carcinoma (TC) is a rare, aggressive cancer without a standardized therapeutic approach in the metastatic context. Recently TCs have been shown to express PD-L1 and respond to single agent immunotherapy. However, small phase II studies have suggested that there may be an increase in severe adverse events. We investigated the role of chemoimmunotherapy (CIO) in a cohort of TC patients in the first line (1L) setting.

Methods

Patient data was retrospectively extracted from the Australian Registry and biObank of thoRAcic cancers (AURORA). Descriptive statistics was used for reports on efficacy and safety. Kaplan Meier analysis was used for overall survival (OS) estimates.

Results

Among 22 TC patients, 17 (77%) with metastatic disease from 3 hospitals were included in this analysis: 9 male, median age 67 years (Q1-Q3 52-72), median follow-up 23.6 months (11.8-39.0), squamous histology (SCC) 11 (65%). Among the 14 systemically treated patients (9 SCC), 8 received standard platinum based chemotherapy and 6 CIO with pembrolizumab in combination with a platinum backbone. Of these, 5 (83%) developed immune-related adverse events (irAE), incl. hypopituitarism, adrenal insufficiency, arthralgia, pneumonitis and skin toxicity. Pneumonitis was the only severe (≥G3) toxicity. No cardiac or neurological irAEs were reported. The objective response rate (ORR) was 50% in the chemo-only group and 67% in the CIO arm. In the CIO group 3 achieved a complete response (CR), 1 a partial response (PR), 1 stable disease (SD) and 1 progressive disease (PD). While 1 of the CR patients achieved remission with CIO alone, the other 2 received additional surgery or SBRT for oligoprogression and have remained in CR thereafter. The median number of pembrolizumab cycles was 17, 2 patients completed 2 years. The median duration of chemo-only response was 9.3 months (2.4 – 17.1) and of CIO response 8.1 months (2.5 – 14.8). Median OS in the chemo-only group was 32.3 months and not reached for the CIO group, with a median follow-up of 24.8 months (13.9-29.2).

Conclusions

CIO is a feasible first line treatment option in metastatic TC. Despite the high frequency of irAEs, only 1 patient had G3 or higher toxicity. With a high ORR and a subset of TC patients achieving durable responses, further studies using 1L CIO in TC are warranted.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

S.E. Bowyer: Financial Interests, Personal, Advisory Board, Cabozantinib ad board: Ipsen; Financial Interests, Personal, Advisory Board, Selpercatinib ad board: Lilly; Financial Interests, Personal, Advisory Board, Cemiplimab ad board: Sanofi; Financial Interests, Personal, Advisory Board, pembrolizumab in H&N cancer Rx: MSD; Financial Interests, Personal, Advisory Board, Neoadjuvant Rx of lung cancer: Roche; Financial Interests, Personal, Invited Speaker, neoadjuvant lung cancer Rx: BMS; Financial Interests, Personal, Invited Speaker, Immunotherapy in lung cancer: MSD; Financial Interests, Personal, Invited Speaker, Cemiplimab in Rx of advanced cutaneous SCC: Sanofi; Non-Financial Interests, Personal, Principal Investigator: BMS, GSK, Genetech, Roche, Enliven Therapeutics Inc, FLX Bio, Lilly, Hummingbird Bioscience, WMBIO, Regeneron, Janssen, ALX Oncology, Replimmune. L. Warburton: Financial Interests, Personal, Advisory Board: Roche, Novartis, MSD, AstraZeneca, BMS. B. Solomon: Financial Interests, Institutional, Advisory Board: AstraZeneca, Novartis, Merck, Bristol Myers Squibb; Financial Interests, Personal, Invited Speaker: Pfizer, AstraZeneca, Roche/Genentech; Financial Interests, Personal, Advisory Board: Amgen, Roche-Genentech, Eli Lilly, Takeda, Janssen; Financial Interests, Personal, Full or part-time Employment, Employed as a consultant Medical Oncologist at Peter MacCallum Cancer Centre: Peter MacCallum Cancer Centre; Financial Interests, Personal, Member of Board of Directors: Cancer Council of Victoria, Thoracic Oncology Group of Australasia; Financial Interests, Personal, Royalties: UpToDate; Financial Interests, Institutional, Steering Committee Member, Principal Investigator and Steering committee Chair: Roche/Genentech, Pfizer; Financial Interests, Institutional, Steering Committee Member: Novartis. T. John: Financial Interests, Personal, Invited Speaker, Speaker tour Vietnam: AstraZeneca; Financial Interests, Personal, Invited Speaker, CTIO: Merck Sharp Dohme; Financial Interests, Personal, Advisory Board: BMS, AstraZeneca, Bayer, Specialised Therapeutics; Financial Interests, Institutional, Advisory Board: Roche, Novartis, Pfizer, Amgen, Takeda, PharmaMar; Financial Interests, Personal, Other, Speaker/Chair: ACE Oncology. All other authors have declared no conflicts of interest.