CameL at 5 years: 1L camrelizumab plus chemo maintains long-term OS benefit

The 5-year update of the phase III CameL study of camrelizumab plus carboplatin and pemetrexed (C+CP) in patients with previously untreated advanced non-squamous non-small-cell lung cancer (NSCLC) without EGFR/ALK alterations demonstrates continued overall survival (OS) and progression-free survival (PFS) benefits.

“Immune checkpoint inhibitors [ICIs] plus platinum-based doublet chemotherapy regimens are well-established first-line therapies for advanced non-squamous NSCLC with no targetable driver mutations,” wrote CameL investigators. [NCCN Clinical Practice Guidelines in Oncology, Non-small-cell lung cancer, version 11.2024; Chin J Oncol 2023;45:539-574] “However, there are limited 5-year survival data to comprehensively evaluate the long-term benefits of these combinations.”

In the randomized, open-label, multicentre, phase III CameL study, Chinese patients with previously untreated non-squamous NSCLC without EGFR/ALK alterations received 4–6 cycles of C+CP (n=205) or CP (n=207) every 3 weeks, followed by maintenance camrelizumab plus pemetrexed or pemetrexed alone. Crossover from the chemotherapy group to camrelizumab monotherapy was permitted after disease progression. [J Immunother Cancer 2024;doi:10.1136/jitc-2024-009240]

At a median follow-up of 65.2 months, the median OS remained longer with C+CP vs CP (27.1 vs 19.8 months; hazard ratio [HR], 0.74; 95 percent confidence interval [CI], 0.58–0.93); one-sided p=0.0043). The respective 5-year OS rates were 31.2 and 19.3 percent. “Consistent with previous reports, the OS benefit with C+CP continued to be observed regardless of age, sex, history of smoking, Eastern Cooperative Oncology Group performance status, brain metastasis status, and tumour PD-L1 expression,” noted the investigators.

In the CP group, 45.9 percent of patients crossed over to receive camrelizumab monotherapy upon radiological progression, and an additional 6.8 percent of patients received subsequent immunotherapy (either alone or combined with other therapies) outside the study, amounting to an effective crossover rate of 52.7 percent. After adjusting for crossover, the median OS for CP was 16.8 months, and the survival benefit was in favour of C+CP, with an HR of 0.62 (95 percent CI, 0.49–0.79; p<0.0001).

At 5 years follow-up, C+CP also continued to show a clinically meaningful improvement over CP in PFS (median, 11.0 vs 6.5 months; HR, 0.55; 95 percent CI, 0.44–0.68; p<0.0001). The 5-year PFS rate was 16.1 percent with C+CP vs 3.0 percent with CP.

Among the 33 patients who completed 2 years of camrelizumab treatment (including maintenance), the median OS had not been reached and the 5-year OS rate was 84.3 percent. The PFS in this subgroup was 60.9 months and the 5-year PFS rate was 57.3 percent.

In the overall population, treatment-related adverse events (TRAEs) of grade ≥3 occurred in 71.2 vs 49.3 percent of patients in the C+CP vs CP group. The most common grade ≥3 TRAEs were haematological toxicities. Serious TRAEs were reported in 38.0 vs 13 percent of patients. Six (2.9 percent) vs three (1.4 percent) deaths were considered to be attributed to TRAEs in the C+CP vs CP groups.

Immune-mediated adverse events (IMAEs) of all grades were reported in 88.8 percent of patients treated with camrelizumab, while 15.6 percent of camrelizumab-treated patients experienced grade ≥3 IMAEs. Reactive cutaneous capillary endothelial proliferation was the most common IMAE; however, the majority (75.1 percent) of cases were grade 1 or 2 in severity.

“In conclusion, C+CP maintained long-term clinically meaningful OS improvement vs CP, despite a high effective crossover rate of 52.7 percent from chemotherapy to immunotherapy. The camrelizumab combination produced an 11.9 percent survival gain at 5 years, while maintaining manageable toxicity,” summarized the investigators.