Camrelizumab Boosts EFS in Nasopharyngeal Carcinomas

Head and neck cancer: © steph photographies - stock.adobe.com

The adjuvant therapy camrelizumab increased the 3-year event-free survival (EFS) rate vs standard of care from 77.3% to 86.9%, translating to a 44% reduced risk of death or relapse in patients with nasopharyngeal carcinoma enrolled in the phase 3 DIPPER trial (NCT03427827; Visual Synopsis). These findings were presented during the American Society of Clinical Oncology Breakthrough Conference, held from August 8 to 10, 2024, in Yokohama, Japan.¹ Camrelizumab also demonstrated mild toxicity with acceptable quality-of- life measures.

“We conducted the DIPPER trial to test the hypothesis that PD-1 blockade will benefit patients with locoregional advanced NPC by improving survival and with manageable toxicity,” Jun Ma, MD, professor, Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China, said during a presentation of the data.

A total of 450 patients with high-risk locoregionally advanced NPC (T4N1M0 or T1-4N2-3M0) who had received gemcitabine and cisplatin plus concurrent chemoradiotherapy were enrolled. After receiving their last radiation dose, patients were randomly assigned 1:1 to receive intravenous camrelizumab (200 mg once every 3 weeks for 12 cycles; camrelizumab arm, n = 226) or observation (standard therapy arm, n = 224). The primary end point was EFS. The secondary end points were overall survival (OS), locoregional relapse-free survival, toxicity profiles, and health-related quality of life.

Historically, anti–PD-1 therapy has been demonstrated to significantly improve progression-free survival in recurrent or metastatic NPC, but its role in the locoregional advanced setting remains minimal.2 Relapse is common among patients who receive standard-of-care treatment of induction chemotherapy and concurrent chemoradiotherapy.

Investigators estimated that approximately 442 patients would provide 80% power to detect an HR of 0.52 with a log-rank test at a 2-sided α level of .05.

The baseline characteristics of the 2 groups were well balanced. In the camrelizumab arm, 97 patients (42.9%) had T3 disease compared with 85 patients (38.0%) in the standard therapy arm. In the camrelizumab arm, 45.1% had T4 disease compared with 46.9% in the standard therapy arm.

“About 30% of patients had stage III disease and 69.9% had stage IV in the camrelizumab arm compared with 31.7% and 68.3%, respectively, in the standard therapy arm,” said Ma, who is also deputy president at Sun Yat-sen University Cancer Center and director, Key Laboratory of Multidisciplinary Diagnosis and Treatment of Nasopharyngeal Carcinoma.

Turning to secondary end points, Ma noted that after a median follow-up after relapse/metastasis of 23.4 months, the 3-year OS rate was 96.4% in the treatment arm vs 92.9% in the control arm (HR, 0.80; 95% CI, 0.35-1.82; P = .587).

“Adverse events [AEs] were mostly grade 1 or 2 and the incidence of grade 3 or 4 all-cause AEs was 11.2% in the camrelizumab arm vs 3.2% in the control arm,” Ma said. Further, only 2.9% of patients in the treatment group discontinued therapy. The most common AE related to camrelizumab was reactive capillary endothelial proliferation (85.8%), followed by peripheral sensory neuropathy (47.3%).

Less than 1% of patients in the camrelizumab group experienced treatment-related deaths (1 patient, subarachnoid hemorrhage) and 1 (< 1%) patient in the standard-therapy group (nasopharyngeal necrosis).

Investigators reported no significant deterioration in quality of life associated with camrelizumab, based on responses to the European Organisation for the Research and Treatment of Cancer Quality of Life Questionnaire.

Ma said the risk of distant metastasis and locoregional relapse is significantly reduced; however, OS between the treatment and control arms was not significantly different and requires longer follow-up. Adverse events are mild with no compromises in health-related quality of life.

“Overall, findings from the DIPPER trial support adjuvant camrelizumab following chemoradiotherapy as a promising strategy for high-risk, locally advanced NPC,” Ma concluded.

REFERENCES:

1. Ma J, Sun Y, Liang YL, et al. Adjuvant PD-1 blockade with camrelizumab in high-risk locoregionally advanced nasopharyngeal carcinoma (DIPPER): a multicenter, open-label, phase 3, randomized controlled trial. J Clin Oncol. 2024;42(suppl 17):LBA6000. doi:10.1200/JCO.2024.42.17_ suppl.LBA6000

2. Mai HQ, Chen QY, Chen D, et al. Toripalimab or placebo plus chemotherapy as first-line treatment in advanced nasopharyngeal carcinoma: a multicenter randomized phase 3 trial. Nat Med. 2021;27(9):1536-1543. doi:10.1038/ s41591-021-01444-0