Cemiplimab prolongs survival in advanced NSCLC with high PD-L1 expression

First-line cemiplimab significantly improved overall survival (OS) and progression-free survival (PFS) in patients with advanced NSCLC* with PD-L1** tumour expression of ≥50 percent, according to the EMPOWER-Lung 1*** study presented at ESMO 2020.

This phase III trial analysed 710 patients with advanced NSCLC, of whom 563 had PD-L1 tumour expression of ≥50 percent. Participants were randomized to receive either intravenous cemiplimab monotherapy 350 mg Q3W (n=356, median age 63.0 years) or physician’s choice of platinum-doublet chemotherapy for 4–6 cycles (n=354, median age 64.0 years). Patients who experienced disease progression on chemotherapy were crossed over to receive cemiplimab alone (n=150), while those who progressed on cemiplimab received extended cemiplimab treatment plus four cycles of chemotherapy (n=50). [ESMO 2020, abstract LBA52]

At a median follow-up of 13.1 months, patients who received cemiplimab had significantly longer OS than those on chemotherapy in the overall ITT population (median 22.1 vs 14.3 months; hazard ratio [HR], 0.68; p=0.0022).

In patients with PD-L1 tumour expression of ≥50 percent, median OS was not reached in the cemiplimab arm and was 14.2 months in the chemotherapy arm (HR, 0.57; p=0.0002) at a median follow-up of 10.8 and 10.2 months, respectively.

Despite the high crossover rate (74 percent), a significant improvement in OS was still achieved among those who progressed on chemotherapy and were crossed over to cemiplimab monotherapy, said Dr Ahmet Sezer from the Department of Medical Oncology at Başkent University in Adana, Turkey.

Patients treated with cemiplimab also demonstrated significantly longer PFS than those treated with chemotherapy in the overall ITT (median 6.2 vs 5.6 months; HR, 0.59; p<0.0001) and PD-L1 ≥50 percent populations (median 8.2 vs 5.7 months; HR, 0.54; p<0.0001).

Objective response rate (ORR) was higher in the cemiplimab vs chemotherapy arm (36.5 percent vs 20.6 percent; p<0.0001 for the overall ITT population and 39.2 percent vs 20.4 percent; p<0.0001 for PD-L1 ≥50 percent population).

The median duration of response was also longer among patients on cemiplimab than those on chemotherapy in the overall ITT (21.0 vs 6.0 months) and PD-L1 ≥50 percent populations (16.7 vs 6.0 months).

A greater reduction in tumour volume was noted with cemiplimab compared with chemotherapy in patients with increasing PD-L1 levels, indicating that patients with the highest PD-L1 tumour expression (≥90 percent) experienced the largest reduction in tumour volume (ORR, 45.9 percent vs 18.1 percent). “Substantial increments for ORRs were seen … [and] survival was better with cemiplimab vs chemotherapy, regardless of [baseline] PD-L1 levels,” Sezer noted.

Grade 3–5 treatment-emergent adverse events occurred at a lower rate in the cemiplimab vs chemotherapy arm (14.1 percent vs 39.2 percent). Deaths occurred in 2.5 and 2.0 percent, respectively. “The safety profile of cemiplimab was consistent with … other PD-L1 inhibitors in NSCLC and other tumour types,” noted Sezer.

“For patients with advanced NSCLC with PD-L1 ≥50 percent and without targetable mutations, anti-PD-1/PD-L1 monotherapy or in combination with chemotherapy are preferred treatment options … [However,] selecting the most effective treatment with favourable toxicity profile [still] remains a challenge,” said Sezer.

“The EMPOWER-Lung 1 study met its primary and secondary endpoints,” Sezer said. “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.”

“Taken together, our data provide the rationale for cemiplimab as a new first-line monotherapy option for patients with advanced NSCLC with PD-L1 ≥50 percent,” he added.

*NSCLC: Non-small cell lung cancer

**PD-L1: Programmed cell death-ligand 1