Camrelizumab when used in combination with gemcitabine, and cisplatin has shown potential as a new standard of care for the frontline treatment of nasopharyngeal carcinoma.
The frontline combination of camrelizumab, gemcitabine, and cisplatin significantly prolonged progression-free survival (PFS) compared with gemcitabine and cisplatin alone in patients with recurrent or metastatic nasopharyngeal carcinoma, according to results from the CAPTAIN-1st study published in Lancet Oncology.1
Findings from CAPTAIN-1st suggest a potential new standard of care for recurrent or metastatic nasopharyngeal carcinoma.
“Our results show that addition of camrelizumab to chemotherapy of gemcitabine plus cisplatin significantly improves the progression-free survival in this patient population. Additionally, the safety profile of this combination therapy is predictable and manageable, wrote the study authors led by Yunpeng Yang, MD, of the Sun Yat-sen University Cancer Center, in Guangzhou, China.
With the current standard of care, platinum-based chemotherapy, the long-term benefit is limited to a 20% 12-month PFS rate, and median overall survival (OS) of just 22.1 months (95% CI, 19.2-25.0).
Developing evidence supports the strategy of adding camrelizumab to platinum-based chemotherapy to enhance the stimulation of the immune response achieved with the current standard.2
CAPTAIN-1st (NCT03707509) randomized, double-blind, placebo-controlled, phase 3 trial was conducted in 28 hospitals throughout China. Those enrolled were between the ages of 18 and 75 with pathologically confirmed nasopharyngeal carcinoma who had metastatic disease or local recurrence after curative radiotherapy that is not treatable with local therapy. The group of patients enrolled also has not received prior systemic therapy for recurrent or metastatic disease and had an ECOG performance status of 0 or 1, an estimated life expectancy of at least 12 weeks, at least 1 measurable lesion, and adequate organ function.
More than 340 patients were assessed for eligibility and 263 were randomized in a 1:1 fashion to received camrelizumab plus gemcitabine and cisplatin or gemcitabine and cisplatin with placebo. In total, 134 patients were treated in the camerlizumab combination arm and 129 were treated in the control arm. The primary end point investigated was PFS by Independent Review Committee (IRC)according to RECIST v1.1. The secondary end points included investigator-assessed PFS, objective response rate, duration of response, 2-year overall survival rate, and safety determined by the number of adverse events (AEs).
The population of patients investigated on treatment with camerlizumab plus gemcitabine and cisplatin or the chemotherapy combination alone had a median age of 49 year (interquartile range [IQR], 40-57) at baseline and largely consisted of male patients. The majority of patients nonkeratinizing undifferentiated histology, and most did not have lung metastases. Liver metastases were common in the population including in 52% of the experimental arm versus 51% of the control arm. Sixty-four percent of patients in each arm received concurrent chemotherapy prior to joining the study.
At a median follow-up of 15.6 months (IQR, 7.7-12.7) at the updated analysis, the median PFS observed with camerlizumab plus gemcitabine and cisplatin was 10.8 months (95% CI, 8.5-13.6) compared with 6.9 months (95% CI, 5.9-7.9) in the chemotherapy arm (HR, 0.51, 95% CI, 0.37-0.69).
Observing the study’s secondary end point in the full analysis set, the objective responses were seen in 87.3% (95% CI 80.5%-92.4%) of the experimental arm compared with in 80.6% (95% Ci, 72.7%-87.1%). The median DOR was longer with the addition of camerlizumab to chemotherapy at 8.5 months (95% CI, 6.9-11.1) verses 5.6 months (95% CI, 5.2-6.9) in the control arm (HR, 0.54; 95% CI, 0.37-0.79). The DCR was similar between the treatment arms at 96.3% (95% CI, 91.5%-98.8%) in the camerlizumab arm versus 94.6% (95% CI, 89.1%-97.8%) in the chemotherapy-only arm.
All patients in the experimental arm and the control arm experienced AEs of any grade, and grade 3 or higher AEs occurred in 94% versus 91%, respectively. The most common grade 3 or higher AEs in the experimental arm versus the control arm, respectively were decreased white blood cell count (66% vs 70%), decreased neutrophil count (64% vs 66%), anemia (40% vs 44%), and decreased platelet count (40% vs 40%).
“To our knowledge, this is the first placebo-controlled, phase 3 study to report the combination of a checkpoint inhibitor, camrelizumab, with gemcitabine and cisplatin in patients with treatment-naive recurrent or metastatic nasopharyngeal carcinoma,” wrote Yang et al.
Further follow-up is required to confirm the benefit of adding camrelizumab or another anti-PD-L1 agent to the combination of gemcitabine and cisplatin as treatment of recurrent or metastatic nasopharyngeal carcinoma.
1. Yang Y, Qu S, Li J, et al. Camrelizumab versus placebo in combination with gemcitabine and cisplatin as first-line treatment for recurrent or metastatic nasopharyngeal carcinoma (CAPTAIN-1st): a multicentre, randomised, double-blind, phase 3 trial. Lancet Oncol. 2021;22(8):1162-1174. doi: 10.1016/S1470-2045(21)00302-8
2. Fang W, Yang Y, and Ma Y et al. Camrelizumab (SHR-1210) alone or in combination with gemcitabine plus cisplatin for nasopharyngeal carcinoma: results from two single-arm, phase 1 trials. Lancet Oncol. 2018; 19: 1338-1350