Treatment with nivolumab plus ipilimumab led to a superior improvement in overall survival (OS) vs standard-of-care chemotherapy in patients with unresectable malignant pleural mesothelioma (MPM), according to the full CheckMate 743 trial dataset, newly published in the Lancet.1
Nivolumab plus ipilimumab was approved by the U.S. Food and Drug Administration (FDA) in October 2020 for the first-line treatment of adults with unresectable MPM based on data from CheckMate 743’s prespecified interim analysis.1,2
The open-label, phase 3 trial (ClinicalTrials.gov Identifier: NCT02899299) randomly assigned 605 patients with newly diagnosed unresectable MPM to receive nivolumab plus ipilimumab or platinum plus pemetrexed chemotherapy. All patients also received folic acid and vitamin B12 one week before their first dose of study treatment. The primary end point was OS; secondary end points included progression-free survival (PFS), objective response rate (ORR), duration of response (DOR), disease control rate, and safety.
At baseline, the median age was 69 years and 77% of patients were male. Fifty-seven percent were current or former smokers. Among the 95% and 98% of patients with quantifiable PD-L1 status in the nivolumab/ipilimumab and chemotherapy arms, respectively, 80% and 74% had PD-L1 expression levels of 1% or greater.
The trial met the specified end point at this interim analysis, and the analysis was therefore considered final.
Nivolumab plus ipilimumab was found to significantly prolong OS, with a median of 18.1 months compared with 14.1 months with chemotherapy (HR, 0.74; 96.6% CI, 0.60-0.91; P =.0020). This translated to 1-and 2-year OS rates of 68% and 41% with nivolumab plus ipilimumab, respectively, compared with 58% and 27% with chemotherapy.
When stratified by histology, the OS benefit with nivolumab plus ipilimumab remained significant for non-epithelioid disease, with a median of 18.1 months compared with 8.8 months with chemotherapy (HR, 0.46; 95% CI, 0.31-0.68). OS was similar between groups among patients with epithelioid histology (HR, 0.86; 95% CI, 0.69-1.08). The OS benefit was also most apparent among patients with PD-L1 expression of 1% or greater (HR, 0.69; 95% CI, 0.55-0.87).
Despite the difference in OS, there was no significant difference in PFS between groups. The median PFS was 6.8 months with nivolumab plus ipilimumab compared with 7.2 months with chemotherapy (HR, 1.00; 95% CI, 0.82-1.21). The 2-year PFS was 16% and 7% with nivolumab plus ipilimumab or chemotherapy, respectively.
The ORR was also similar between the groups (nivolumab/ipilimumab, 40% vs chemotherapy, 43%). The median DOR was longer with immunotherapy (11.0 months vs 6.7 months).
The rates of any-grade and grade 3 to 4 adverse events (AEs) were similar between groups; however, any-grade serious AEs occurred more frequently with nivolumab plus ipilimumab (21% vs 8%). Treatment-related AEs led to treatment discontinuation in 23% of patients in the nivolumab plus ipilimumab arm compared with 16% of patients in the chemotherapy arm.
The study authors concluded, “first-line nivolumab plus ipilimumab provided a significant and clinically meaningful improvement in OS versus platinum plus pemetrexed chemotherapy.” They added that this regimen “should be considered as a new standard of care for previously untreated patients with unresectable MPM, regardless of histological subtype.”
Disclosures: Some of the study authors disclosed financial relationships with the pharmaceutical industry and/or the medical device industry. For a full list of disclosures, please refer to the original study.
- Baas P, Scherpereel A, Nowak AK, et al. First-line nivolumab plus ipilimumab in unresectable malignant pleural mesothelioma (CheckMate 743): a multicentre, randomised, open-label, phase 3 trial. Lancet. 2021;397(10272):375-386. doi: 10.1016/S0140-6736(20)32714-8
- FDA approves nivolumab and ipilimumab for unresectable malignant pleural mesothelioma [press release]. Silver Spring, MD: FDA; October 2, 2020. Accessed February 2, 2021.