Cemiplimab prolongs OS in NSCLC with high PD-L1 expression
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Cemiplimab-rwlc monotherapy extended OS compared with first-line platinum doublet chemotherapy for certain patients with advanced non-small cell lung cancer, according to study findings presented at ESMO Virtual Congress 2020.
Results of the randomized phase 3 EMPOWER-Lung 1 trial — which included patients whose tumors had PD-L1 expression of 50% or higher — showed cemiplimab (Libtayo; Sanofi, Regeneron) reduced risk for death by more than 30%.
“These results support cemiplimab as a potential new option for anti-PD-1 monotherapy in first-line advanced NSCLC,” Ahmet Sezer, MD, associate professor in the department of medical oncology at Baskent University in Turkey, told Healio. “In addition to potentially offering a new first-line monotherapy option for patients with [at least] 50% PD-L1 expression, cemiplimab is supported by a pivotal trial data set that could help address outstanding questions facing physicians in real-world clinical practice.”
Immunotherapy has greatly improved outcomes for patients with advanced NSCLC. However, given the heterogeneity of the disease, additional emphasis must be placed on identifying the most appropriate therapies for specific patient subsets — including the estimated 25% to 30% of patients who have high PD-L1 expression.
“Patients with NSCLC represent a diverse population that come to us from many different backgrounds, and many have comorbidities, as well,” Sezer said. “There is still a lot we don’t know, and more research is needed — especially in optimizing chemotherapy-free treatment options for patients whose tumors have high PD-L1 expression.”
Cemiplimab — a fully human monoclonal antibody that targets PD-1 — is approved in the United States for treatment of adults with metastatic cutaneous squamous cell carcinoma or locally advanced cutaneous squamous cell carcinoma who are not candidates for curative surgery or curative radiation.
The open-label, multicenter EMPOWER-Lung 1 trial compared the agent with platinum doublet chemotherapy as first-line therapy for patients with locally advanced or metastatic NSCLC with PD-L1 expression in at least 50% of tumor cells.
The trial included 710 adults with stage IIIB or stage IIIC NSCLC — all of whom were not candidates for surgical resection or definitive chemoradiation or had progressed after chemoradiation — or previously untreated stage IV NSCLC.
EMPOWER-Lung 1 was designed “to reflect current and emerging treatment paradigms,” Sezer said.
Twelve percent of patients had pretreated and stable brain metastases. Eligibility criteria also allowed patients with squamous or nonsquamous histology to enroll, as well as those with controlled hepatitis B, hepatitis C or HIV.
Researchers randomly assigned patients 1:1 to cemiplimab dosed at 350 mg via IV every 3 weeks for up to 108 weeks (n = 356) or investigator’s choice of standard platinum-based doublet chemotherapy for four to six cycles, with or without maintenance pemetrexed (n = 354).
Upon disease progression, patients assigned chemotherapy could cross over to cemiplimab, and those assigned cemiplimab had the opportunity to continue treatment with that agent in combination with four cycles of chemotherapy.
Treatment groups were well-balanced with regard to median age (63 years for cemiplimab vs. 64 years for chemotherapy), sex (men, 87.6% vs. 83.1%), region of enrollment (Europe, 77.2% vs. 78.5%), ECOG performance status (0, 27% vs. 27.1%; 1, 73% vs. 72.9%), histology (nonsquamous, 55.3% vs. 57.1%) and presence of brain metastases (12.4% vs. 11%).
OS and PFS as assessed by blinded independent review committee served as primary endpoints. Secondary endpoints included overall response rate, duration of response and quality of life.
The independent review committee performed a protocol-specified interim analysis after 50% of OS events occurred.
Median follow-up in the intention-to-treat population was 13.1 months.
Results showed cemiplimab significantly prolonged PFS (6.2 months vs. 5.6 months; HR = 0.59; 95% CI, 0.49-0.72) and OS (22.1 months vs. 14.3 months; HR = 0.68; 95% CI, 0.53-0.87) in the intention-to-treat population.
Researchers also analyzed outcomes among the 563 patients (cemiplimab, n = 283; chemotherapy, n = 280) in the intention-to-treat population with at least 50% PD-L1 expression as determined by use of the PD-L1 IHC 223C pharmDx assay (Agilent).
Median follow-up for this group was 10.8 months. Results showed cemiplimab significantly extended median PFS (8.2 months vs. 5.7 months; HR = 0.54; 95% CI, 0.43-0.68) and median OS (not reached vs. 14.2 months; HR = 0.57; 95% CI, 0.42-0.77).
“It was very encouraging to see that cemiplimab significantly improved OS compared with chemotherapy,” Sezer told Healio. “What was notable was that this result was achieved despite the 74% crossover rate of patients to the cemiplimab group following disease progression on chemotherapy.”
Researchers reported the OS and PFS benefits across all patient subgroups, except for those enrolled in Asia. Increasing PD-L1 expression levels correlated with better outcomes among patients assigned cemiplimab, Sezer said.
Outcomes in the intention-to-treat population favored cemiplimab with regard to response rate (36.5% vs. 20.6%; P < .0001) and median duration of response (21 months vs. 6 months).
Cemiplimab appeared well-tolerated despite considerably longer treatment exposure with the experimental therapy than chemotherapy (median, 27.3 weeks vs. 17.7 weeks), and researchers observed no new safety signals.
A higher percentage of chemotherapy-treated patients experienced treatment-related adverse events (any grade, 88.6% vs. 57.5%; grade 3 or higher, 39.2% vs. 14.1%).
However, a higher percentage of patients assigned cemiplimab experienced treatment-related adverse events that led to treatment discontinuation (any grade, 5.1% vs. 3.5%; grade 3 or higher, 2.5% vs. 2.3%) or death (any grade, 2.5% vs. 2%; grade 3 or higher, 2.5% vs. 2%).
The most common adverse events reported among patients assigned cemiplimab included anemia (14.6% for cemiplimab vs. 94.2% for chemotherapy), decreased appetite (11.8% vs. 18.4%), fatigue (10.1% vs. 17%), pneumonia (9.3% vs. 10.8%), constipation (7.6% vs. 15.2%) and nausea (6.2% vs. 28.4%).
The most common grade 3 or higher adverse events reported among patients assigned cemiplimab included pneumonia (4.8% for cemiplimab vs. 5.6% for chemotherapy) and anemia (3.4% vs. 16.4%).
Results of EMPOWER-Lung 1 will form the basis of regulatory submissions in the United States and Europe.
“Cemiplimab is also being studied in combination with chemotherapy in a pivotal trial [that includes] patients with advanced NSCLC irrespective of PD-L1 expression,” Sezer said. “That trial is now fully enrolled, and initial data are expected in 2021. I’m looking forward to seeing the results.”
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Sezer A, et al. Abstract LBA52. Presented at: European Society for Medical Oncology Virtual Congress 2020; Sept. 19-21, 2020.
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