First-Line Camrelizumab Plus Gemcitabine Combo Could Become a New Standard for Nasopharyngeal Carcinoma

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.

Reference

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