The anti-PD-1 antibody spartalizumab demonstrated promising responses in patients with recurrent/metastatic nasopharyngeal cancer.
Although spartalizumab (Arzerra) did not meet its primary end point of progression-free survival (PFS), the agent elicited a longer overall survival (OS) and duration of response (DOR) vs chemotherapy in patients with non-keratinizing recurrent/metastatic nasopharyngeal cancer (NPC), according to findings from a phase 2 study (NCT02605967) published in Clinical Cancer Research.
Investigators reported a median OS was 25.2 months (95% CI, 13.1–not estimable [NE]) compared with 15.5 months (95% CI, 8.3-21.3) in the chemotherapy arm. Additionally, patients experienced a median DOR of 10.2 months (95% CI, 7.4-NE) in the experimental arm vs 5.7 months (95% CI, 3.7-7.4) in the chemotherapy arm.
“Treatment with spartalizumab was generally well tolerated in this phase 2 study with no unexpected safety concerns. The primary efficacy endpoint of median PFS was not met. However, the median OS and median DOR, as per RECIST v1.1, were both longer in patients who received spartalizumab compared with those who had chemotherapy. The long duration of response with spartalizumab treatment compared with chemotherapy suggests a preliminary long-lasting antitumor effect of spartalizumab in [ nasopharyngeal cancer],” the study’s investigators wrote.
A total of 122 patients were randomized as of the data cutoff. The study included 4 groups of patients, including the spartalizumab arm (n = 82), the chemotherapy arm (n = 40), the crossover arm, and the all spartalizumab group. Investigators reported that 80.5% (n = 66) of patients in the spartalizumab arm, 92.5% (n = 37) in the chemotherapy arm, and 88.0% (n = 22) in the crossover arm had discontinued treatment primarily due to disease progression.
In total, 27 of 39 patients in the chemotherapy arm were treated with single agent chemotherapy and 12 patients received a chemotherapy combination of 2 or more drugs. Twenty five of the 40 patients in the chemotherapy arm crossed over to the spartalizumab arm following confirmation of radiologic progression.
Prior to the study, all patients had received antineoplastic therapies, with radiotherapy being the most common in the spartalizumab and chemotherapy arms, respectively (84.1% vs 92.5%). Additionally, 80.5% of patients in the spartalizumab arm received more than 2 prior systemic therapies in any setting compared with 77.5% in the chemotherapy arm. Moreover, the most common prior therapy in the spartalizumab (84.0%) and chemotherapy arms (82.5%) was cisplatin. Approximately 48% to 58% of patients were previously treated with carboplatin, flouracil, or gemcitabine.
In the spartalizumab arm, 6.1% (n = 5) of patients had a complete response compared with 7.5% (n = 3) in the chemotherapy arm. A partial response was reported in 22.0% (n = 18) and 25.0% (n = 10) of patients in the spartalizumab and chemotherapy arms, respectively. Progressive disease was reported in 34.1% (n = 28) and 20.0% (n = 8) of patients in the spartalizumab and chemotherapy arms, respectively.
The median PFS in the spartalizumab arm was 1.9 months (95% CI, 1.8-3.6) compared with 6.6 months (95% CI, 3.7-9.3) in the chemotherapy arm (HR, 1.36: 95% CI, 0.87-2.21; P = .915). Those who crossed over from chemotherapy to spartalizumab had a median PFS of 1.7 months (95% CI, 1.6-1.9).
Among patients who were treated with chemotherapy and did not cross over, the OS was 17.6 months (95% CI, 4.2-NE). The overall response rate (ORR) in the spartalizumab arm was 17.1% (95% CI, 9.7%-27.0%) compared with 35.0% (95% CI, 20.6%-51.7%) in the chemotherapy arm. In the spartalizumab arm, the disease control rate was 42.7% (95% CI, 31.8%-54.1%) and 70% (95% CI, 53%.5-83.4%) in the chemotherapy arm.
Serious adverse effects (SAEs) of all grades suspected to be related to treatment were identified in 11.2% (n = 12) of patients in the all-spartalizumab arm compared with 17.9% (n = 7) of patients in the chemotherapy arm.
As of special interest included increases liver enzymes that were grade 3 or 4, which occurred in 4.7% (n = 5) patients. One patient in the crossover arm that developed grade 3 pneumonitis and was the only AE of special interest that led to discontinuation.
In the all spartalizumab arm compared with the chemotherapy arm, (1.9% vs 10.3%) AEs leading to discontinuation were less frequent. In total, 6.1% (n = 5) of in the spartalizumab arm, 7.7% (n = 3) in the chemotherapy arm, and 12% (n = 3) in the crossover group had died, none of which were related to treatment.
Even C, Wang HM, Li SH, et al. Phase II, Randomized study of spartalizumab (PDR001), an anti-PD-1 antibody, versus chemotherapy in patients with recurrent/metastatic nasopharyngeal cancer. Clin Cancer Res. Published online, August 25, 2021. doi:10.1158/1078-0432.CCR-21-0822