The American Society for Clinical Oncology’s (ASCO) annual meeting concluded last week in Chicago, IL. As the largest oncology meeting in the world, ASCO is often where researchers announce research updates and new data.
This year, we were very interested in one study in particular – the Phase 3 Randomized Study of Pembrolizumab in Patients with Advanced Malignant Pleural Mesothelioma, also referred to as IND.227. We already covered the Phase 2 results of this trial, and in March of 2023, we reported that Merck announced that its Phase 3 counterpart was positive and that data would be forthcoming.
This study is one of the first completed studies looking into the efficacy of the combination of chemotherapy with immunotherapy. Since 2004, the chemotherapy regimen of pemetrexed (Alimta) and cisplatin was the only standard of care until 2020, when the FDA approved the immunotherapy combination of nivolumab and ipilimumab (Opdivo/Yervoy), making it only the second standard of care for the treatment of mesothelioma. In the last few years, the question has been whether combining these two standards can create an added benefit beyond what each treatment can do as a stand-alone.
Several studies were initiated to answer this question, most notably the DREAM (Phase 2) followed by the DREAMER (Phase 3) studies, and also, in the UK and Europe, the BEAT-meso study which adds bevacizumab to chemotherapy and immunotherapy, and, finally, IND.227, the results of which we cover in this write-up.
The IND.227 protocol included 440 patients enrolled in Canada, France, and Italy, who were randomly assigned to two different groups. One group was treated with standard chemotherapy (Alimta/cisplatin or carboplatin) AND pembrolizumab (Keytruda). The second group was only treated with standard chemotherapy. All patients were treatment naïve, meaning that they had not received any previous treatment. Pembrolizumab is an immune checkpoint inhibitor that binds to the PD-1 protein found on T cells which, by doing so, signals to the immune system to attack the cancer cell.
The study results didn’t see an association between benefit and levels of PD-L1 expression, which is in line with results from previously reported immunotherapy studies.
Ultimately, overall survival (OS) was this study’s primary endpoint. The median OS was 17.28 months for patients treated with both chemotherapy and immunotherapy and 16.13 months for those treated only with chemotherapy.
Consistent with data from other immunotherapy studies, patients with sarcomatoid or biphasic mesothelioma appeared to gain the most from the addition of immunotherapy. In fact, these patients saw an improvement in median overall survival of over four months, while epithelioid patients’ improvement in median overall survival was 1.6 months.
The differences in benefits between different subtypes of mesothelioma reinforce the notion that different types of mesotheliomas should be treated with different approaches based on these data. Moreover, as clinicians work with patients on treatment decisions, the increased toxicity profile of this combination will need to be considered. In this case, chemotherapy plus pembrolizumab might not be the best option for all patients, but it could be an option for some. As such, the focus on patient selection by the mesothelioma medical community seems to be a hopeful next step.
