Cemiplimab shows favourable signals as first-, second-line treatment alternative for NSCLC

In the 3-year follow-up of the EMPOWER-Lung 1 study, first-line cemiplimab continued to outdo chemotherapy (CT) in providing survival benefit for patients with advanced non-small-cell lung cancer (NSCLC). Moreover, in the second-line setting (patients with progressive disease [PD]), cemiplimab added to CT provided meaningful and durable objective response rate (ORR) and overall survival (OS) benefit.

The intention-to-treat (ITT) cohort comprised 712 participants (median age 64 years, 85 percent male, 84 percent stage IV disease). Of these, 565 had PD-L1 ≥50 percent. Participants in the ITT cohort were randomized 1:1 to receive cemiplimab 350 mg IV Q3W (for 108 weeks or until PD) or 4–6 CT cycles (investigator’s choice). Those on cemiplimab who were confirmed to have PD had the option to continue cemiplimab, plus CT (up to four cycles). CT recipients were given the option to cross over to cemiplimab monotherapy in the event of PD. [ESMO 2022, abstract LBA54]

As first-line therapy

After a median follow-up of 37.1 months, median OS in the ITT population was significantly longer with cemiplimab vs CT (23.4 vs 13.7 months; hazard ratio [HR], 0.63), as was median progression-free survival (PFS; 6.3 vs 5.3 months; HR, 0.56; p=0.0001 for both).

The significant survival benefit was also seen in the subgroup of patients with PD-L1 ≥50 percent (median, 26.1 vs 13.3 months; HR, 0.57 [OS] and median, 8.1 vs 5.3 months; HR, 0.51 [PFS]; p=0.0001 for both).

The OS improvement was achieved despite a 75-percent crossover rate, noted Dr Mustafa Özgüroğlu from Istanbul University-Cerrahpaşa, Istanbul, Turkey, at ESMO 2022. “[This is] an exceptional finding in the NSCLC field,” he stressed.

Cemiplimab also induced higher ORRs vs CT, both in the ITT (42 percent vs 21 percent; odds ratio [OR], 2.69) and PD-L1 ≥50-percent populations (46 percent vs 21 percent; OR, 3.26; p<0.0001 for both). Duration of response was longer with cemiplimab vs CT (23.6 vs 5.9 months [both ITT and PD-L1 ≥50-percent cohorts]).

The rate of grade 3–5 treatment-emergent adverse events (TEAEs) leading to discontinuation was higher with cemiplimab vs CT (6 percent vs 3 percent). The most common grade 3–5 TEAE associated with cemiplimab use was pneumonia (5 percent), followed by anaemia (4 percent) and dyspnoea (3 percent).

These findings showed further and significant improvement in the initially observed OS and PFS benefit of cemiplimab monotherapy vs CT in these patients, said Özgüroğlu. “[Taken together,] these results support the importance of cemiplimab as first-line non-CT treatment for patients with advanced/metastatic NSCLC and those with PD-L1 ≥50 percent.”

Beyond progression

In the post-PD analysis (n=64; median age 62 years, 86 percent male, 81 percent stage IV disease), the cemiplimab-CT regimen yielded a 31-percent ORR, which was primarily driven by those having a partial response (27 percent). More than half (55 percent) of the patients had stable disease.

Median OS was 15.1 months. This finding is nearly twofold higher than that seen in a previous study on second-line CT showing a median OS of 8.4 months, noted Özgüroğlu.

In this subgroup, 36 percent of patients reported grade 3–5 AEs, the most common being anaemia (9 percent), diarrhoea (3 percent), and neutropenia (3 percent).

This is the first report from a phase III study showing the therapeutic advantage of cemiplimab-CT for patients who have progressed following first-line PD1 monotherapy, said Özgüroğlu. “The durable ORR and OS benefits compare favourably with historical data of patients receiving CT alone as second-line therapy (after immune-checkpoint inhibitor monotherapy).”