MHRA Approves BMS’s Opdivo Plus Yervoy for First-Line Treatment of Unresectable Malignant Pleural Mesothelioma

Compiled and Translated by | Fan Dongdong

Recently, the UK Medicines and Healthcare products Regulatory Agency (MHRA) approved Bristol-Myers Squibb's (BMS) blockbuster immunotherapy combination of Opdivo (nivolumab) and Yervoy (ipilimumab) for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM).

This regulatory victory also signifies that the Opdivo and Yervoy combination immunotherapy has the opportunity to expand into new indication markets. The MHRA’s positive decision regarding the Opdivo and Yervoy combination regimen was primarily based on supportive data from the ongoing Phase III CheckMate-743 trial. This open-label, multicenter, randomized Phase III study compared the efficacy and safety of Opdivo plus Yervoy versus standard chemotherapy (pemetrexed in combination with cisplatin or carboplatin) in patients with previously untreated malignant pleural mesothelioma.

Trial results showed that at a minimum follow-up of 22.1 months, the median overall survival (OS) in the Opdivo plus Yervoy immunotherapy combination arm was 18.1 months, compared with 14.1 months in the chemotherapy arm. The Opdivo and Yervoy immunotherapy combination reduced the risk of death by 26% in patients with unresectable malignant pleural mesothelioma, extending OS by 4 months. Furthermore, the combination therapy demonstrated higher and more sustained overall survival rates compared to chemotherapy, with 1-year OS rates of 68% and 58%, respectively. The difference in 2-year OS was more pronounced, at 41% and 27%, respectively.

In the trial, the safety profile of the Opdivo and Yervoy combination immunotherapy was consistent with previously reported study results, with no new safety signals observed. The incidence rates of treatment-related adverse events (TRAEs) of any grade for the Opdivo and Yervoy combination immunotherapy were 80% and 82%, respectively, with grade 3–4 adverse events occurring in 30.3% of patients, which is comparable to the 32.0% rate in the chemotherapy group. The most common adverse reactions (≥15%) in the Opdivo and Yervoy combination immunotherapy group were diarrhea and pruritus, whereas in the chemotherapy group, they were nausea, anemia, neutropenia, fatigue, decreased appetite, and asthenia.

The Opdivo and Yervoy combination immunotherapy comprises two immune checkpoint inhibitors with a potential synergistic mechanism of action. It targets two distinct checkpoints (PD-1 and CTLA-4) in a complementary manner to help destroy tumor cells. To date, this combination therapy has been approved for multiple cancer indications, including melanoma, renal cell carcinoma, colorectal cancer, hepatocellular carcinoma, non-small cell lung cancer, and malignant pleural mesothelioma.

In addition to malignant pleural mesothelioma, the Opdivo and Yervoy immunotherapy combination has recently achieved regulatory breakthroughs in other indications. In June, the UK National Institute for Health and Care Excellence (NICE) recommended this combination immunotherapy for the treatment of patients with advanced colorectal cancer following failure of fluoropyrimidine-based chemotherapy who harbor rare microsatellite instability-high (MSI-H) or mismatch repair deficient (dMMR) alterations. However, this year, the combination immunotherapy failed to meet its primary endpoint in the Phase 3 CheckMate-651 trial for squamous cell carcinoma of the head and neck.

Source: MHRA approves Opdivo plus Yervoy for unresectable malignant pleural mesothelioma