Camrelizumab Yields ‘Impressive’ Activity in Head & Neck Cancer Subtype

Investigators observed impressive clinical activity following treatment with camrelizumab plus apatinib in refractory recurrent or metastatic nasopharyngeal carcinoma, according to findings from a phase 2 clinical trial (NCT04586088).

“[The] study of apatinib and camrelizumab shows quite impressive results as a single arm study in recurrent/metastatic nasopharynx cancer,” according to an expert from Memorial Sloan Kettering Cancer Center.

In the intent-to-treat population (n = 58), the objective response rate (ORR) was 65.5% (95% CI, 51.9%-77.5%), which included a complete response rate of 22.4% and a partial response rate of 43.1%. Additionally, the disease control rate was 86.2% (95% CI, 74.6%-93.9%), and 96.2% of patients experienced tumor shrinkage in target lesions.

The median time to response was 2.1 months (interquartile range, 1.4-3.1), and the median duration of response (DOR) was not reached. Additionally, 68.4% (95% CI, 51.4-82.5%) of patients had responses that lasted at least 6 months, and 65.8% (95% CI, 48.7%-80.4%) of responses were ongoing.

“[The] study of apatinib and camrelizumab shows quite impressive results as a single arm study in recurrent/metastatic nasopharynx cancer,” Eric J. Sherman, MD, stated in a written comment to CancerNetwork^® on the trial data. “The results are even more impressive since all patients had at least one line of prior treatment.”

However, Sherman, a medical oncologist at Memorial Sloan Kettering Cancer Center who wasn’t involved in the trial, noted some important limitations to the study and described how the findings may be relevant to patient care in the United States.

“First, it is only a single arm study, so the results need to be confirmed in a multicenter study,” Sherman stated. “Second, this was done in an Epstein-Barr virus [EBV]–associated cancer population. In the United States, a significant proportion of nasopharynx cancer is not driven by EBV, so we do not know if these data will apply to non-EBV–related nasopharynx cancer. Third, the standard of care in the first line has changed so that most patients with recurrent/metastatic nasopharynx cancer will receive chemotherapy and immunotherapy in the first line.

He also noted that resistance to PD-1 antibodies in the second-line setting could make the regimen unsuitable for patients. Despite these limitations of the study, Sherman nevertheless wrote that the results are grounds for further research.

“The results are impressive enough to warrant doing a first line randomized study against gemcitabine, platinum-based chemotherapy, and a PD-1 antibody,” Sherman stated.

Investigators of this single-arm, stage 2 study assessed camrelizumab plus apatinib among patients with treatment-naïve, recurrent or metastatic nasopharyngeal carcinoma. Patients received 250 mg of apatinib orally once a day plus 200 mg of camrelizumab intravenously once every 3 weeks until disease progression, unacceptable toxicities, patient withdrawal, or death.

The primary end point of the study was ORR based on RECIST v1.1 criteria. Secondary end points included progression-free survival (PFS), overall survival (OS), DOR, DCR, and safety.

Patients 18 to 70 years old with histologically confirmed nasopharyngeal carcinoma refractory to at least 1 line of systemic chemotherapy or who had disease progression within 6 months following induction, concurrent, or adjuvant chemoradiotherapy were eligible for enrollment. Additional inclusion criteria included having an ECOG performance status of 0 or 1 and at least 1 measurable lesion.

Overall, 43.1% of patients had locoregional recurrence only, 31.0% had distant metastases only, and 25.9% had both locoregional recurrence and metastases. All patients received at least 1 prior line of therapy and 17.2% received at least 2 prior lines.

With a median follow-up of 12.4 months (range 2.1-19.9), 29 patients discontinued study treatment, including 26 who had disease progression and 3 who had unacceptable adverse effects (AEs).

The median PFS was 10.4 months (95% CI, 7.2-13.6). Additionally, PFS was 44.3% (95% CI, 29.5%-58.6%) at 12 months.

In terms of OS, 13.8% of patients died and the median OS was not reached. Additionally, the 18-month OS rate was 85.7% (95% CI, 76.2%-95.0%).

The ORR for patients with locoregional recurrence only and for those with metastatic lesions, respectively, was 80.0% and 54.5% (P = .043). The DOR for those with metastatic lesions demonstrated a positive trend that was not statistically significant (HR, 0.54; 95% CI, 0.16-1.78; P = .308), and the PFS of those with locoregional recurrence only and metastatic lesions was comparable (HR, 1.11; 95% CI, 0.53-2.33; P = .784).

Grade 3 or higher treatment-related AEs (TRAEs) occurred in 58.6% of patients, with the most common including hypertension (19.0%), nasopharyngeal necrosis (15.5%), headaches (12.1%), creatine phosphokinase increase (10.3%), and aspartate aminotransferase increase (10.3%). Additionally, 27.6% of patients discontinued apatinib treatment prior to disease progression due to unacceptable TRAEs; of these patients, the most common AE was nasopharyngeal necrosis, occurring in 56.3% of patients.

Investigators indicated a significant positive correlation between recurrent nasopharyngeal lesions (odds ratio [OR], 5.94; 95% CI, 1.45-24.24) and reirradiation (OR, 5.33; 95% CI, 1.15-24.79) with nasopharyngeal necrosis.

Reference

Ding X, Zhang W, You R, et al. Camrelizumab plus apatinib in patients with recurrent or metastatic nasopharyngeal carcinoma: an open-label, single-arm, phase 2 study. J Clin Oncol. Published online February 3, 2023. doi:10.1200/JCO.22.01450