Survival, PROs Favor Cemiplimab Plus Chemotherapy vs Chemotherapy Alone in Advanced NSCLC

Cemiplimab plus chemotherapy not only showed favorable survival benefits for patients with non–small cell lung cancer (NSCLC) compared with chemotherapy alone,¹ but the combination also resulted in significant improvements based on patient-reported outcomes (PROs),² according to posters presented at ESMO Congress 2023.

Cemiplimab plus chemotherapy was approved by the FDA to treat adults with advanced non–small cell lung cancer based on earlier results from EMPOWER-Lung 3.

Image credit: pakorn - stock.adobe.com

The EMPOWER-Lung 3 study analyzed cemiplimab in combination with chemotherapy in patients with advanced squamous and nonsquamous NSCLC with any level of PD-L1 expression. Patients were randomized in a 2:1 fashion to receive either cemiplimab 350 mg every 3 weeks plus investigator’s choice of platinum-doublet chemotherapy (n = 217) or chemotherapy alone (n = 110) every 3 weeks up to 108 weeks or disease progression. The majority (70.2%) of patients had PD-L1 levels ≥ 1% and 46.5% of the overall study population had PD-L1 expression ≥ 50%.

Earlier results from EMPOWER-Lung 3 were used as the basis for FDA’s approval of cemiplimab plus platinum-based chemotherapy to treat adults with advanced NSCLC whose tumors did not harbor EGFR, ALK, or ROS1 aberrations.³

The first poster presented efficacy and safety for patients with approximately 2 years of follow-up.¹ The combination significantly improved median overall survival (OS) and progression-free survival (PFS) over chemotherapy. The median OS for the combination was 23.5 months (95% CI, 20.9-27.2) vs 12.1 months (95% CI, 10.1-15.7) for chemotherapy alone. The median PFS was 8.3 months (95% CI, 6.7-10.8) for the combination compared with 5.5 months (95% CI, 4.3-6.2).

The objective response rate (ORR) was 47.9% for the combination with a 5.1% complete response and 42.9% partial response. The ORR was 22.7% for chemotherapy alone, with no complete responses. The median duration of response was 17.5 months for the combination vs 6.5 months for chemotherapy alone.

ORR, median OS, and median PFS were all significantly higher for cemiplimab plus chemotherapy vs chemotherapy alone in patients with squamous and nonsquamous NSCLC. In squamous NSCLC, ORR was 45.3% for the combination vs 25.5% for chemotherapy, median OS was 23.2 months for the combination vs 12.6 months for the chemotherapy, and median PFS was 8.2 months for the combination vs 4.6 months for the chemotherapy alone. In nonsquamous NSCLC, ORR was 50.0% for the combination vs 20.3% for the chemotherapy, median OS was 23.5 months for the combination vs 12.1 months for the chemotherapy, and median PFS was 10.3 months for the combination vs 6.2 months for the chemotherapy alone.

The safety profile of patients with PD-L1 expression was consistent patients without PD-L1 expression. Grade ≥ 3 treatment-emergent adverse events (TEAEs) occurred in 48.4% of patients with PD-L1 expression and 48.7% of overall patients treated with the combination and 27.5% of patients with PD-L1 expression and 32.7% of overall patients treated with chemotherapy alone.

The most common TEAEs of any grade in the combination arm were anemia (47.0%), alopecia (37.3%), and nausea (25.3%). The most common TEAEs of any grade in the chemotherapy alone arm were alopecia (44.0%), anemia (35.8%), and increased alanine transaminase (13.8%).

There were 14 (6.5%) TEAEs of any grade that led to treatment discontinuation in the combination arm and 4 (3.7%) in the chemotherapy arm. There were 14 (6.5%) TEAEs that led to death in the combination arm and 8 (7.3%) in the chemotherapy arm.

The second poster evaluated PROs for the same group of patients in the first poster and found an improved benefit to patients receiving cemiplimab plus chemotherapy vs chemotherapy alone.² PROs were assessed at baseline, followed by Day 1 of each of the first 6 treatment cycles, and finally on Day 1 of every third cycle. PROs were assessed using the European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life-Core 30 (QLQ-C30) and Quality of Life-Lung Cancer 13 (QLQ-LC13). Time to definitive clinically meaningful deterioration (TTD) was assessed using a 10-point threshold.

The baseline means scores were similar across both arms. Results showed a significant delay in TTD favoring the combination for physical functioning, role functioning, nausea/vomiting, pain, dyspnea, coughing, sore mouth, and alopecia. The results also showed emotional functioning and global health status/quality of life favored the combination.

By PD-L1 subgroup:

• PD-L1 < 1% had significant delays in TTD favoring the combination in cognitive functioning and hemoptysis
• PD-L1 1-49% had significant delays in TTD in physical, role, and emotional functioning, as well as symptoms of fatigue, nausea/vomiting, dyspnea, and dysphagia
• PD-L1 ≥ 50% had significant delays in TTD in role functioning and symptoms of dyspnea, coughing, hemoptysis, and sore mouth

Mixed model for repeated measures analyses also showed significant overall improvement in pain from baseline scores. There were no symptom scales from QLQ-C30 and QLQ-LC13 that favored the chemotherapy alone arm.

“PRO results further support the favorable benefit–risk profile of cemiplimab,” the researchers concluded.

References

1. Baramidze A, Makharadze T, Baramidze A, et al. Cemiplimab plus chemotherapy versus chemotherapy in non-small cell lung cancer with PD-L1 ≥1%: EMPOWER-Lung 3 results. Ann Oncol. 2023;34(suppl_2):S755-S851. doi:10.1016/annonc/annonc1331

2. Gogishvili M, Melkadze T, Baramidze A, et al. Patient-reported outcomes (PROs) with cemiplimab plus chemotherapy (CEMI + CHEMO) for first-line treatment of advanced non-small cell lung cancer (aNSCLC): PD-L1 level subgroups in EMPOWER-Lung 3. Ann Oncol. 2023;34(suppl_2):S755-S851. doi:10.1016/annonc/annonc1331

3. FDA approves cemiplimab-rwlc in combination with platinum-based chemotherapy for non-small cell lung cancer. FDA. November 8, 2022. Accessed November 21, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/