Brigette B.Y. Ma, MD
Nivolumab (Opdivo) induced an overall response rate (ORR) of 20.5% in patients with recurrent or metastatic nasopharyngeal carcinoma (NPC), according to results from the phase II NCI-9742 study.
The median overall survival (OS) was 17.1 months (95% CI, 10.9–not reached) and the 1-year OS rate was 59% (95% CI, 44.3-78.5), which compared favorably to previous study results.
“In these [other] studies, the 1-year OS rates were consistently reported at approximately 45% to cytotoxic and noncytotoxic drugs. In a recently published phase Ib study of 27 patients with a mixed background of treatment-naïve or pretreated squamous and nonsquamous NPC, treatment with pembrolizumab resulted in a response rate of 25.9% and 1-year OS of 63%,” first author Brigette B.Y. Ma, MD, Department of Clinical Oncology, Prince of Wales Hospital, Hong Kong, and colleagues wrote.
“Compared with those in that phase Ib study, the patients in our study were all treatment refractory, nearly all had detectable plasma EBV DNA at baseline, and >80% had nonkeratinizing NPC that was more reflective of endemic NPC,” added Ma et al.
Forty-four patients with histologically or cytologically confirmed NPC that had recurred at locoregional and/or distant sites and were not amenable to curative treatment were included in this analysis. The enrollment period ran from October 28, 2015, to June 1, 2016.
The median follow-up was 12.5 months (range, 2.2-22.0) for the 28 patients who were still alive at the July 10, 2017, data cutoff. The majority of the cohort (82.2%) identified as Asian in this multicenter, international study. Median age was 57.0 years (range, 37.0-76.0).
Patients received 3 mg/kg of nivolumab every 2 weeks on a 4-week cycle until disease progression.
One (2.3%) patient had a complete response lasting >12 months. Eight (18.2%) had a partial response with a median duration of response of 9.3 months (95% CI, 3.6-13.1 months) and 15 (34.1%) had stable disease. Eighteen (40.9%) patients had disease progression and 2 (4.5%) were not assessed for response. The disease control rate was 54.5%.
Investigators found no correlation between the number of prior lines of chemotherapy and the response pattern to the last line of chemotherapy before enrollment.
The median progression-free survival (PFS) was 2.8 months (95% CI, 1.8-7.4), with a 1-year PFS rate of 19.3% (95% CI, 10.1-37.2).
Thirteen (29.5%) patients were still receiving treatment 6 months after registration, and 9 (20.5%) received treatment for >12 months.
In a preplanned biomarker study, archived, paraffin-embedded NPC tumors were retrieved for the immunohistochemical analysis of PD-L1 protein expression. PD-L1 expression of <1% was regarded as negative and expression of ≥1% was regarded as positive.
Investigators retrieved archived tumors from 42 patients and prospectively collected plasma samples from 43 patients for biomarker analysis. There was no statistical difference between patients with PD-L1–negative versus PD-L1–positive tumors in terms of OS or PFS.
Six (33%) of 18 patients with PD-L1–positive tumors responded to nivolumab compared with 3 (13%) patients with PD-L1–negative tumors, but the difference did not reach statistical significance.
Forty-one samples were of sufficient quality to determine HLA expression. Investigators noted a statistical difference in PFS between patients with tumors showing loss of expression of HLA-A and/or HLA-B and patients with tumors expressing both HLA-A and HLA-B at 1-year (30.9% vs 5.6%). The same was true for median PFS (4.8 vs 1.8 months).
Median OS was not reached in patients with tumors exhibiting loss of expression of HLA-A and/or HLA-B expression compared with 10.9 months (95% CI, 9.7–not evaluable) for patients with tumors expressing both HLA-A and HLA-B. The 1-year OS rate favored patients who lost expression (75.7% vs 33.8%). However, the difference was not statistically significant (log-rank P
There was no association between HLA expression and response rate (HLA-A and HLA-B expressed, 22.22%, vs HLA-A and/or HLA-B loss, 19.23%; Fisher P
Patients received a median of 3 cycles of nivolumab (range, 1-19). The leading cause of permanent discontinuation was disease progression (69.2%). Roughly 10% of patients discontinued for adverse events (AEs).
Of the 45 patients who were evaluable for toxicities, 10 (22.2%) experienced grade ≥3 AEs that were possibly related to nivolumab. Grade ≥3 toxicities included colitis, diarrhea, fatigue, increase in aspartate transaminase or alanine aminotransferase levels, neutropenia, hyponatremia, and lymphopenia. One patient died of pulmonary tuberculosis during treatment.
Ma BBY, Lim WT, Goh BC, et al. Antitumor activity of nivolumab in recurrent and metastatic nasopharyngeal carcinoma: an international, multicenter study of the mayo clinic phase 2 consortium (NCI-9742) [published online March 27, 2018]. J Clin Oncol. doi: 10.1200/JCO.2017.77.0388.