1067P - The interchangeability of Immune checkpoint inhibitors

Background

Immune checkpoint inhibitors (ICIs) are used for the treatment of various tumours. They are amongst the best-selling cancer drugs. The introduction of several new ICIs in the past few years has not resulted in price competition. From clinical and societal perspectives, it is worthwhile to investigate whether the six available ICIs are therapeutically interchangeable. If so, this may facilitate use and stimulate price reduction by competition.

Methods

We investigated by means of a literature review, whether the ICIs for the indications with the greatest expenditure and number of patients, namely lung cancer and melanoma, are being interchangeable. Due to the lack of direct comparative studies we conducted a systematic search in PubMed, Embase en de Cochrane Library to identify all eligible (network)meta-analyses (NMA) until November 2022. Literature search terms used were “network meta-analysis” ’PD[L] 1” AND non small lung carcinoma AND melanoma. Only NMA’s including randomized clinical trials that compared the efficacy (overall survival and progression free survival) and safety (treatment related side-effects) of the PD-(L)1 inhibitors nivolumab, pembrolizumab, atezolizumab, durvalumab and/or cemiplimab with or without chemotherapy to chemotherapy were eligible.

Results

A total of 3 NMA’s involving patients with advanced NSCLC were included, and one NMA involving not-previously treated patients with advanced melanoma. Where indications do overlap - mainly monotherapy – no studies with head-to-head comparisons of ICIs have been conducted. By indirect comparison of evidence, no clinically relevant differences in effectiveness and safety are apparent. However, the validity of these indirect comparisons have strong limitations, due to the differences in inclusion criteria and patient characteristics.

Conclusions

We conclude that the determination of interchangeability of ICIs is complicated due to the limited overlap in authorized indications and lack of direct comparison between ICIs. Where indications do overlap, we expect that any differences will have limited clinical significance. We call for (publicly funded) randomized multi-cancer trials for a direct head-to-head comparison of ICIs. Such direct comparative evidence is needed to reach a competitive field.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

Dutch Health Care Institute.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.