1918P - Real-world efficacy and toxicity of combination immunotherapy in mesothelioma: North East of England experience

Background

Combination immunotherapy with Nivolumab and Ipilimumab (N+I) is approved as the first-line treatment option for mesothelioma following the Checkmate 743 trial (CM 743). The aim of this study was to evaluate the efficacy and toxicity of N+I in real world practice in an area with a high incidence of asbestos related malignancy.

Methods

Data of patients treated with N+I between 2018 and 2023 in first- and subsequent-line settings from two large Oncology centres in the North East of England was collected retrospectively. Toxicity was graded according to Common Terminology Criteria for Adverse Events (CTCAE). The Kaplan−Meier method was used to estimate mOS and PFS.

Results

A total of 80 patients were identified: median age was 75(58-91), 88% were male, 100% were ECOG ≤1. 95% were pleural vs 5% peritoneal subtype. Within the pleural group, 66% were epithelioid, 26% biphasic, 8% sarcomatoid.

N+I was used as first-line treatment in 80% vs 14% as second-line and 6% as third line. The median number of cycles received were 3(1-15) for both N+I. Best response was PR in 28%, SD in 25%, PD 37% and not evaluated in 10%.

Median PFS for our population was 6.8 months (ms) (95%CI), with 7, 4.3 and 9.8 ms in those who had N+I as first, second and third line respectively. mOS was 10.8 ms (95%CI) with 10.2, 15.9, 11.4 ms in the first, second and third line respectively. There was no statistically significant difference in mOS for epithelioid compared with non-epithelioid histology (95%CI) with OS 13.4, 9.4 ms respectively.

G1/2 toxicity was noted in 40% of patients compared to 49% in CM 743. G3/4 was noted in 30% of patients, similar to CM 743, and 0% with G5 versus 1% in CM743. 24% required oral steroid treatment, 19% required IV steroid and 7.5% required additional immune suppression such as infliximab/immunoglobulin.

Reasons for treatment discontinuation were disease progression in 39%, toxicity in 31% and decline in fitness in 18%.

Conclusions

We observed a mOS of 10.8 ms which is lower than the Checkmate 743 trial and a real-world dataset from Australia (McNamee et al., JTO, 2023). Toxicity was similar to the trial data but the exposure was significantly less with 3 cycles (1-15) for N+I compared to 12 (5-23) for N and 4 (2-7) for I in CM743.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Newcastle upon Tyne NHS trust.

Funding

Has not received any funding.

Disclosure

A. Greystoke: Financial Interests, Personal, Advisory Board: BMS, AstraZeneca, Boehringer Ingelheim, Takeda, Roche, Novartis; Financial Interests, Personal, Invited Speaker: Merck, MSD, Pfizer, Janssen; Financial Interests, Institutional, Local PI: MSD; Financial Interests, Institutional, Coordinating PI: Pfizer, AstraZeneca, Novartis, Achilles; Non-Financial Interests, Advisory Role: National Institue for Health and Clinical Excellence; Non-Financial Interests, Leadership Role, Steering Committee member: British Thoracic Oncology Group; Other, Clinical Lead for Cancer (paid position): North East Englad and Yorkshire Genomic Laboratory Hub. All other authors have declared no conflicts of interest.