medwireNews: Cemiplimab monotherapy offers a significant overall survival (OS) benefit compared with platinum-doublet chemotherapy for advanced non-small-cell lung cancer (NSCLC) patients with a PD-L1 tumor cell expression of 50% or above, indicate initial EMPOWER-Lung 1 trial findings.
“Taken together, our data provide the rationale for cemiplimab as a new first-line monotherapy option” for this population, presenting author Ahmet Sezer, from Bașkent University in Adana, Turkey, told delegates at the ESMO Virtual Congress 2020.
For the phase 3 trial, 356 patients were randomly assigned to receive cemiplimab 350 mg every 3 weeks followed by cemiplimab and four cycles of chemotherapy at time of first progression, while 354 participants were given 4–6 cycles of a physician’s choice of chemotherapy, with the option to crossover to cemiplimab at time of progression
At the time of the second interim analysis, the median treatment duration was 27.3 weeks for the cemiplimab arm and 17.7 weeks for those given chemotherapy, with 31.6% of 158 patients who progressed on cemiplimab continuing with cemiplimab and chemotherapy, and 73.9% of the chemotherapy-assigned participants crossing over to cemiplimab monotherapy.
After a median 13.0 months of follow-up, OS in the intention-to-treat (ITT) population was a median 22.1 months with cemiplimab versus 14.3 months with chemotherapy, giving a significant hazard ratio (HR) for death of 0.68 in favor of cemiplimab treatment.
The OS of a subgroup of 563 patients – with a PD-L1 level of 50% or greater on a test meeting the trial’s strict criteria – also significantly favored cemiplimab after approximately 10.0 months of follow-up, with the median unreached versus 14.2 months and a HR of 0.57.
Progression-free survival (PFS) was also significantly better with cemiplimab than chemotherapy for both the ITT population (6.2 vs 5.6 months, HR=0.59) and the confirmed PD-L1 of 50% or higher subgroup (8.2 vs 5.7 months, HR=0.54).
Subgroup analysis indicated that OS and PFS both favored use of cemiplimab when patients were assessed by age, sex, region, ECOG performance score, histology, baseline presence of brain metastases, and cancer stage at screening. The exception was for patients located in Asia whose OS favored chemotherapy but Sezer said that “the number of events in this subgroup was too small to draw any conclusions.”
Among the patients with a confirmed PD-L1 score of at least 50% given cemiplimab, the investigators found that the change in target tumor volume significantly and positively correlated with increasing baseline PD-L1 expression. By contrast, no such correlation was found in the chemotherapy arm.
Similarly, the objective response rate (ORR) was higher with cemiplimab than chemotherapy for both the ITT (36.5 vs 20.6%) and the confirmed PD-L1 50% or greater subgroup (39.2 vs 20.4%), and duration of response also mirrored this pattern, at a median of 21.0 versus 6.0 months and 16.7 versus 6.0 months, respectively.
Moreover, the ORR correlated with PD-L1 expression in the cemiplimab arm, peaking for patients with a PD-L1 level of 90% or higher, at 45.9% versus 18.1% for those given chemotherapy. The OS and PFS curves also correlated with PD-L1 expression in the cemiplimab arm but not the chemotherapy-treated patients.
“Despite substantially longer exposure to cemiplimab, the safety profile and patient-reported [health-related quality of life] support the positive benefit–risk profile of cemiplimab,” Sezer commented.
Analysis of global health status and health-related quality of life (HRQoL) in the ITT population indicated that cemiplimab was associated with a 10-point increase in score from baseline to the end of treatment, indicating a “clinically meaningful improvement” in this measure, whereas no such benefit was apparent with chemotherapy.
Safety analysis indicated that treatment-related adverse events were less common with cemiplimab than chemotherapy overall (57.5 vs 88.6%) and at grade 3–5 (14.1 vs 39.2%).
Adverse events with cemiplimab were consistent with those previously reported for the agent and other PD-L1 inhibitors, commented Sezer. The most common grade 3–5 events with cemiplimab were pneumonia (4.8%) and anemia (3.4%) versus anemia (16.4%) and neutropenia (10.2%) with chemotherapy.
“Despite substantially longer exposure to cemiplimab, the safety profile and patient-reported HRQoL support the positive benefit–risk profile of cemiplimab,” Sezer concluded.
Discussing the EMPOWER-Lung 1 findings at the meeting, Roy Herbst, from Yale Cancer Center in New Haven, Connecticut, USA, praised the study for having a “real-world population” of smokers and patients with stable brain metastases, the latter of whom with a confirmed PD-L1 of at least 50% experienced a significant benefit with cemiplimab.
Noting the study also allowed cemiplimab-treated patients to begin chemotherapy after progression, he now looks forward to the results for the ongoing INSIGNIA study of first-line immunotherapy alone or alongside chemotherapy for NSCLC after progression.
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