The combination of nivolumab plus ipilimumab becomes the first new therapy approved for patients with mesothelioma in 15 years.
The FDA approved nivolumab (Opdivo) in combination with ipilimumab (Yervoy) for the first-line treatment of adult patients with unresectable malignant pleural mesothelioma (MPM),
according to Bristol Myers Squibb.
The approval was based on efficacy results from a pre-specified interim analysis from the open-label, multi-center, randomized phase 3 CHECKMATE 743 (NCT02899299) trial, designed to evaluate nivolumab plus ipilimumab compared with chemotherapy (pemetrexed and cisplatin or carboplatin) in patients with histologically confirmed unresectable MPM and no prior systemic therapy or palliative radiotherapy within 14 days of initiation of therapy. 1
With a minimum of 22.1 months of follow-up, the immunotherapy combination demonstrated superior overall survival (OS), compared with the standard chemotherapy arm (HR, 0.74; 95% CI, 0.61-0.89; P = .002), with a median OS of 18.1 months (95% CI, 16.8-21.5) versus 14.1 months (95% CI, 12.5-16.2), respectively. Two-year OS was 41% with nivolumab plus ipilimumab, compared with 27% with chemotherapy.1,2
A total of 303 patients were randomized to receive 3 mg/kg nivolumab every 2 weeks and 1 mg/kg ipilimumab every 6 weeks, while 302 patients were randomized to receive 75 mg/m2 cisplatin or 500 mg/m2 carboplatin area under the curve 5 plus pemetrexed in 3-week cycles for 6 cycles until disease progression or unacceptable toxicity or, in the combination arm, up to 24 months.
The primary end point was OS in all randomized patients. Secondary end points included progression-free survival (PFS), objective response rate (ORR) and duration of response (DOR).
Median PFS for the immunotherapy arm, per blinded independent central review (BICR), was 6.8 months (95% CI, 5.6-7.4) and 7.2 months (95% CI, 6.9-8.1) in the standard chemotherapy arm (HR 1.0; 95% CI ,0.82- 1.21). Confirmed ORR per BICR was 40% (95% CI, 34%-45%) and 43% (95% CI, 37%-49%) in the nivolumab plus ipilimumab and chemotherapy arms, respectively. Median DOR was 11.0 months for patients receiving the immunotherapy combination compared with just 6.7 months in the chemotherapy arm.
Although the interim analysis from CHECKMATE 743 showed improvements in survival rates in both nonepithelioid and epithelioid malignant pleural mesothelioma, patients with a nonepithelioid histology derived the larger benefit. Median OS for this subgroup was 18.1 months (HR, 0.46; 95% CI, 0.31-0.68) with the dual immunotherapy combination compared with 8.8 months for those patients receiving standard chemotherapy. At 24 months, OS was 38% for those patients with nonepithelioid histology who received the immunotherapy combo, versus 8% for those receiving the standard chemotherapy treatment.3
In the immunotherapy arm, 23% of patients discontinued treatment due to adverse events (AEs) and 52% had at least 1 dose withheld for an AE. Moreover, 4.7% of patients permanently discontinued ipilimumab alone due to AEs. The most frequent grade 3/4 AEs included pneumonia, pyrexia, diarrhea, pneumonitis, pleural effusion, dyspnea, acute kidney injury, infusion-related reaction, musculoskeletal pain, and pulmonary embolism.2
This approval represents the first and only immunotherapy treatment approved for this patient population and comes 6 weeks after the submission of a new supplemental biologics license application.2
1. FDA approves nivolumab and ipilimumab for unresectable malignant pleural mesothelioma. US Food & Drug Administration. October 2, 2020. Accessed October 9, 2020. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-nivolumab-and-ipilimumab-unresectable-malignant-pleural-mesothelioma
2. US Food and Drug Administration approves Opdivo (nivolumab) + Yervoy (ipilimumab) as the first and only immunotherapy treatment for previously untreated unresectable malignant pleural mesothelioma. News release. Bristol Myers Squibb. October 2, 2020. Accessed October 11, 2020. https://news.bms.com/news/details/2020/U.S.-Food-and-Drug-Administration-Approves-Opdivo-nivolumab--Yervoy-ipilimumab-as-the-First-and-Only-Immunotherapy-Treatment-for-Previously-Untreated-Unresectable-Malignant-Pleural-Mesothelioma/default.aspx.
3. Fowler M. Nivolumab plus ipilimumab improves OS in malignant pleural mesothelioma. CancerNetwork. August 10, 2020. Accessed October 11, 2020. https://www.cancernetwork.com/view/nivolumab-plus-ipilimumab-improves-os-in-malignant-pleural-mesothelioma