Investigators identified an improvement in median progression-free survival among patients with recurrent or metastatic nasopharyngeal carcinoma who were treated with camrelizumab plus gemcitabine and cisplatin vs placebo plus gemcitabine.
The benefit observed from the use of first-line camrelizumab (SHR-1210) plus gemcitabine and cisplatin in patients with recurrent or metastatic nasopharyngeal carcinoma could lead to the regimen becoming a new standard of care treatment, according to data from a randomized phase 3 trial (NCT03707509) published in Lancet Oncology.
The median progression-free survival (PFS) as assessed by an independent review committee for the camrelizumab cohort was 9.7 months (95% CI, 8.3-11.4) compared with 6.9 months in the placebo group (95% CI, 5.9-7.3). The survival benefit achieved with the experimental combination was determined to be statistically significant (HR, 0.54; 95% CI, 0.39-0.76; one-sided P = .0002).
“To our knowledge, this is the first placebo-controlled, phase 3 study to report the combination of a checkpoint inhibitor, camrelizumab (anti-PD-1), with gemcitabine and cisplatin in patients with treatment-naïve recurrent or metastatic nasopharyngeal carcinoma,” the study authors wrote. “Our results show that addition of camrelizumab to chemotherapy of gemcitabine plus cisplatin significantly improves the [PFS] in this patient population.”
A total of 343 eligible patients screened between November 13, 2018, and November 29, 2019, 263 of whom were randomized to either the camrelizumab regimen (n = 134) or placebo plus gemcitabine (n = 129). All patients received at least 1 dose of treatment and were included in the efficacy and safety analyses. The median patient age was 49 years (interquartile range [IQR], 40-57). Additionally, the majority of patients had non-keratinizing undifferentiated histology and two-thirds had received concurrent chemoradiotherapy. All patients included on the study had distant metastases. The median follow-up duration at the data cutoff point was 10.2 months (IQR, 7.7-12.7).
Treatment regimens included either a 200 mg dose of camrelizumab on day 1 or matching placebo administered intravenously, plus gemcitabine at a dose of 1000 mg/m2 on days 1 and 8 and 80 mg/m2 of cisplatin on day 1 intravenously every 3-week cycle for 4 to 6 cycles. This was followed by maintenance therapy with camrelizumab alone or placebo on day 1 of every 3-week cycle until radiographic progression or unacceptable toxicity.
Eligible patients were aged 18 to 75 years with pathologically-confirmed nasopharyngeal carcinoma and primary metastatic disease or local recurrence after curative radiotherapy. Patients also could not have received previous therapy and needed to have an ECOG performance score of 0 or 1.
When assessing objective responses, which were evaluated via independent review committee, investigators reported that 87.3% (95% CI, 80.5%-92.4%) of patients in the camrelizumab group and 80.6% (95% CI, 72.7%-87.1%) of patients in the placebo group achieved an objective response. The median duration of response (DOR) was 8.5 months (95% CI, 6.9-11.1) and 5.6 months (95% CI, 5.2-6.9] in the camrelizumab and placebo groups, respectively (HR, 0.54; 95% CI, 0.37-0.79).
Investigators reported that the median investigator-assessed PFS was 12.0 months (95% CI, 9.9-14.0) in the camrelizumab group compared with 7.0 months (95% CI, 6.8-8.3) in the placebo group (HR, 0.49; 95% CI, 0.36-0.67). Overall survival (OS) data were immature for both treatment groups. Median OS was not reached (NR) vs 22.6 months (95% CI, 19.2-NR) in the camrelizumab and placebo groups, respectively (HR, 0.67; 95% CI, 0.41-1.11).
All patients included in the study experienced any grade adverse effects (AEs), with 94% of patients in the camrelizumab group and 91% of patients in the placebo group experiencing grade 3 or higher AEs. Common grade 3 or higher AEs in patients who received the camrelizumab and placebo regimens, respectively, included 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%). Seven percent of patients in the camrelizumab group and 5% of patients in the placebo group experienced AEs that led to death.
Serious treatment-related AEs were observed in 36% and 29% of patients in the camrelizumab and placebo groups, respectively. The most common treatment-related serious AE was decreased platelet count in 14% of patients in the camrelizumab group and 16% of patients in the placebo group.
“Camrelizumab plus gemcitabine and cisplatin could be a new standard of care for patients with recurrent or metastatic nasopharyngeal carcinoma in the first-line setting. However, longer follow-up is needed to confirm this conclusion,” the investigators concluded.
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