IASLC World Conference on Lung Cancer
IASLC World Conference on Lung Cancer
Perspective from Dean A. Fennell , PhD, FRCP
Perspective from Howard (Jack) West, MD
Source:

Baas P, et al. Abstract LBA 3. Presented at: International Association for the Study of Lung Cancer World Conference on Lung Cancer Virtual Presidential Symposium; Aug. 8, 2020.


Disclosures: Bristol-Myers Squibb funded this study. Baas reports advisory board roles with AstraZeneca, Merck Sharp & Dohme and Takeda. Please see the abstract for all other researchers’ relevant financial disclosures.

August 10, 2020
3 min read
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First-line nivolumab-ipilimumab combination improves OS in mesothelioma subset

Perspective from Dean A. Fennell , PhD, FRCP
Perspective from Howard (Jack) West, MD
Source:

Baas P, et al. Abstract LBA 3. Presented at: International Association for the Study of Lung Cancer World Conference on Lung Cancer Virtual Presidential Symposium; Aug. 8, 2020.


Disclosures: Bristol-Myers Squibb funded this study. Baas reports advisory board roles with AstraZeneca, Merck Sharp & Dohme and Takeda. Please see the abstract for all other researchers’ relevant financial disclosures.

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First-line nivolumab plus ipilimumab significantly extended OS compared with platinum-based chemotherapy for patients with unresectable malignant pleural mesothelioma, according to results of an interim analysis of the CheckMate 743 trial.

Paul Baas, MD, researcher at Netherlands Cancer Institute and University of Leiden in Amsterdam, presented the results during the International Association for the Study of Lung Cancer World Conference on Lung Cancer Virtual Presidential Symposium.

First-line nivolumab plus ipilimumab significantly extended OS compared with platinum-based chemotherapy for patients with unresectable malignant pleural mesothelioma.
First-line nivolumab plus ipilimumab significantly extended OS compared with platinum-based chemotherapy for patients with unresectable malignant pleural mesothelioma.

“We have been trying to improve the OS of patients with mesothelioma for many decades,” Bass said during the presentation. “CheckMate 743 met its primary endpoint of statistically improved OS with nivolumab plus ipilimumab vs. standard-of-care chemotherapy in first-line treatment of patients with mesothelioma. These clinically meaningful data represent the first positive phase 3 trial of immunotherapy in first-line malignant pleural mesothelioma and should be considered as a new standard of care.”

Five-year survival rates for malignant pleural mesothelioma, a highly aggressive cancer, remain below 10%, according to researchers. The combination of nivolumab (Opdivo, Bristol-Myers Squibb), which restores antitumor T-cell function, and ipilimumab (Yervoy, Bristol-Myers Squibb), which targets CTLA-4, has shown promising activity in single-arm studies for this patient population.

Paul Baas, MD, PhD
Paul Baas

Bass and colleagues analyzed the combination among 605 adults with previously untreated, unresectable, histologically confirmed malignant pleural mesothelioma and an ECOG performance status 0 or 1. Researchers randomly assigned patients to 3 mg/kg nivolumab once every 2 weeks plus 1 mg/kg ipilimumab once every 6 weeks for up to 2 years (n = 303) or platinum-based doublet chemotherapy with 75 mg/kg2 cisplatin or carboplatin area under the curve 5 plus 500 mg/m2 pemetrexed (n = 302) for six cycles.

Patients in the immunotherapy and chemotherapy groups had similar baseline characteristics, including median age (69 years for both), percentage of men (77% for both) and histology (epithelioid, 76% vs. 75%).

OS served as the primary endpoint. Secondary endpoints included objective response rate, disease control rate and PFS.

Median follow-up was 29.7 months.

Results showed a higher rate of 2-year OS with the immunotherapy combination vs. chemotherapy (41% vs. 27%). Median OS was 18.1 months (95% CI, 16.8-21.4) with immunotherapy vs. 14.1 months (95% CI, 12.4-16.2) with chemotherapy (HR = 0.74; 95% CI, 0.6-0.91).

The immunotherapy combination conferred superior median OS for patients with an epithelioid histotype (18.7 months vs. 16.5 months; HR = 0.86; 95% CI, 0.69-1.08), those with a nonepithelioid histotype (18.1 months vs. 8.8 months; HR = 0.46; 95% CI, 0.31-0.68) and those with tumor PD-L1 expression of 1% or greater (18 months vs. 13.3 months; HR = 0.69; 95% CI, 0.55-0.87).

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Researchers reported an ORR of 40% with immunotherapy vs. 43% with chemotherapy, a disease control rate of 76.6% vs. 85.1%, and median PFS of 6.8 months vs. 7.2 months (HR = 1; 95% CI, 0.82-1.21).

“Looking at PFS, we know from experience that the way tumors grow that PFS may be difficult to interpret in some cases,” Baas said. “Within the first 6 months, the chemotherapy arm performs a little better, but then the curves cross and the advantage is for the immunotherapy arm."

Baas also acknowledged that the response rates were very similar in both groups.

“In the chemotherapy arm, only partial responses were observed,” he said. “For the immunotherapy arm, 2% of patients had a complete response — these complete responses were a great advantage for the immunotherapy arm with 32% of patients at 2 years still having no signs of progression.”

Grade 3 or grade 4 treatment-related adverse events occurred among 30.3% of patients in the immunotherapy combination group, of whom 15% discontinued treatment, compared with 32% of patients in the chemotherapy arm, of whom 7.4% discontinued treatment.

“We observed a survival benefit with nivolumab plus ipilimumab vs. chemotherapy, regardless of histology,” Baas said. “Nivolumab plus ipilimumab performed similarly in both histologies, [whereas] chemotherapy performed better in epithelioid histology. In addition, PD-L1 data were descriptive in nature, precluding firm conclusions.”