Data from the highly anticipated PROMISE-meso trial failed to deliver, with no PFS or OS benefit seen for pembrolizumab compared to standard chemotherapy.
The Phase III trial involved 144 patients with advanced pre-treated mesothelioma who were randomised to pembrolizumab (200 mg every three weeks) or chemotherapy (gemcitabine/vinorelbine). Patients in the control group were able to cross over to pembrolizumab at progression.
Patients treated with pembrolizumab (Keytruda) had a median progression-free survival (PFS) of 2.5 months compared to 3.4 months with standard chemotherapy regimens (p=0.76). Analysis of PFS by PD-L1 expression status also showed no advantage for pembrolizumab.
Median overall survival was 10.7 months for pembrolizumab vs 11.7 months for chemotherapy (p=0.85).
Treatment-related adverse events grade ≥3 were experienced by 19% of patients in the pembrolizumab group and 24% in the chemotherapy group, one fatal in each group.
Lead researcher Dr Sanjay Popat from the Royal Marsden Hospital NHS Foundation Trust, London, UK, said that while the results were disappointing, nearly four times more patients responded to immunotherapy than standard chemotherapy (ORR was 22% in patients treated with pembrolizumab compared to 6% with chemotherapy (p=0.004).
“If we can find out how this happens, we will have a better idea of which patients should preferentially receive this treatment over chemotherapy,” he said.
Dr. Popat explained that new checkpoint inhibitor studies are needed in patients with earlier stages of mesothelioma than those in PROMISE-meso. Studies also need to investigate the potential of combining immunotherapy with other anti-cancer drugs.
“In studies of lung cancer, we have already learned that we can improve results with immunotherapy by combining it with chemotherapy and the same may be true with mesothelioma. I would advise clinicians to enroll their patients into one of the large ongoing trials of first-line combination treatment so we can get answers as soon as possible about how to improve mesothelioma treatment,” said Popat.
Invited discussant Dr. Federica Grosso, from the Mesothelioma and Rare Cancers Unit, Azienda Ospedaliera SS Antonio e Biagio e Cesare Arrigo, Alessandria, Italy noted that patients with mesothelioma generally died within two years of diagnosis and there was currently no standard effective second line therapy.
“Although we did not see better survival with immunotherapy in the PROMISE-meso study, the responses are encouraging and the results of the ongoing trials of checkpoint inhibitor treatment in earlier stage mesothelioma will be very important to patients and clinicians. We very much need better first and second-line treatment for mesothelioma around the world,” she concluded.