EMPOWER-Lung3: Cemiplimab Combination Therapy in Non–Small Cell Lung Cancer
Expert perspective on the EMPOWER-Lung3 clinical trial, which combined cemiplimab with chemotherapy as frontline treatment for patients with advanced NSCLC.
Transcript:
Jason Porter, MD: EMPOWER-Lung 3 is a phase III trial that included 466 patients who had locally advanced or metastatic non–small cell lung cancer [NSCLC] squamous or nonsquamous histology. They could have any PD-L1 expression level and did not have actionable alterations in EGFR, ALK, or ROS1. The patients had good ECOG [Eastern Cooperative Oncology Group] performance status of 0 or 1, and it was stratified by PD-L1 expression level as less than 1% to 49% or greater than equal to 50%. The histology as well as a stratification variable, nonsquamous vs squamous. The primary end points for this trial were overall survival. Key secondary end points were PFS [progression free survival], objective response rate, the duration of response, and the patient-reported outcomes. In arm A, the patients were given cemiplimab 350 mg Q [every] 3 weeks as we did in our sample patient, [which was] the investigator’s choice of platinum doublet chemotherapy as well with 4 cycles. In arm B, they were given a placebo plus the investigator’s choice of platinum doublet chemotherapy. They were treated for 108 weeks until the disease progressed and then followed up closely.
The overall survival for those patients was a primary end point. What we saw when those patients were treated with cemiplimab plus chemotherapy compared to chemotherapy alone was that the overall survival median was 21.9 months in the intervention arm and 13.0 months in the chemotherapy alone arm. So those patients did much better. We saw a significant improvement in overall survival for those patients.
One key characteristic of the patient population was that the patients were predominantly male. This clinical trial was performed in a European nation where females usually don’t smoke. We know that squamous cell carcinoma is closely aligned with smoking status, and so those patients were mostly male. The median age was about 65 to 65 years. We saw a nice mix of squamous vs nonsquamous histology in that clinical trial. Over 40% of the patients in this trial had squamous cell disease, which is very important. We know already that the outcomes for patients with squamous cells are usually not as good, so it’s nice to have a sizable patient population with squamous cell histology so that we can see exactly how effective the therapies can be when they’re given to these patients who have a poor prognosis.
Another important patient characteristic from the clinical trial is that the patients were not excluded from viral illnesses such as hepatitis or HIV. We know that none of the patients enrolled in a trial had those illnesses, but it was nice that this clinical trial did include those patients. We also saw patients who had locally advanced disease, which was nonmetastatic. In many of our patients who had the nonmetastatic disease because of their respiratory status or other comorbidities, they’re not candidates for definitive therapy such as surgery or concurrent chemoradiation. So it’s nice that this clinical trial included patients who were nonmetastatic but had locally advanced disease and were not candidates for definitive therapy.
When we look at the clinical trial options for first-line therapies for patients who have the metastatic squamous disease, we have CheckMate 9LA, also KEYNOTE-407, and now EMPOWER-Lung 3. In CheckMate 9LA, about 32% of the patients in the patient population had the squamous disease vs 68% with nonsquamous histology. And still, we see overall survival benefit at 27% vs 19% with chemotherapy alone at 3 years, for those patients who were treated with nivolumab and ipilimumab plus platinum doublet. In EMPOWER-Lung 3, we know that about 40% to 45% of those patients have the squamous disease, and the median overall survival was 21.9 months vs 13.0 months for patients who were treated with chemotherapy alone. Similarly, in the KEYNOTE-407 trial, we have 5-year overall survival data now, and the overall survival was 18.4% vs 9.7% for those patients who had the squamous disease, and all patients in KEYNOTE-407 again had the squamous disease.
Overall, the outcomes for these patients in all 3 of these large phase 3 trials are comparable. Regardless of the histology, we see overall survival benefits for these patients. With EMPOWER-Lung 3, again, the size of the squamous cell population is actually encouraging. It’s nice to see such a sizable squamous cell population in a clinical trial of this size. It gives the confidence to know that the selection of this treatment regimen in a squamous cell population is going to be effective. With the patients having liver metastases, such as a patient from our clinical scenario, it’s encouraging because the EMPOWER-Lung 3 trial did include about 10% of patients who had liver metastases. Again, when you’re applying these [trials] in clinical practice, you want to know what the data from the clinical trial show for the patient population that you’re selecting.
Transcript edited for clarity.
