Share this entry
Nivolumab in patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) was associated with a 1-year overall survival (OS) rate of 59% (95% CI, 44.3-78.5) which compares favorably with historic results. This was concluded by the investigators of the collaborative Phase II NCI-9742 study conducted in Hong Kong, Singapore and the United States (US).
Comparative data in similar populations have consistently reported 1-year OS rates of ~45% for both cytotoxic and non-cytotoxic drugs. A recently published Phase Ib study in 27 treatment-naïve or pretreated squamous and non-squamous NPC patients resulted in a 1-year OS rate of 63%.
The study recruited 44 treatment-refractory patients with loco-regional or distant recurrences and who were not amenable to curative treatment. Most participants (82.2%) were of Asian ancestry with histologically or cytologically confirmed NPC. Over 80% of subjects were found to have non-keratinizing NPC, which is reflective of endemic NPC. The median age was 57.0 (37.0-76.0) years. Almost all subjects had detectable plasma EBV-DNA at baseline.
Participants in the NCI-9742 study received 3 mg/kg of nivolumab every two weeks on a 4-week cycle until progression disease. The median duration of treatment was 3 (1-19) cycles. For the 28 patients still alive at the data cut-off, the median follow-up was 12.5 (2.2-22.0) months.
Figure 1. Response rates with nivolumab in advanced nasopharyngeal carcinoma (NPC) in the NCI-9742 study
Nivolumab in patients with recurrent or metastatic nasopharyngeal carcinoma (NPC) was associated with a 1-year OS rate of 59% (95% CI, 44.3-78.5). The median overall survival (OS) was 17.1 months (95% CI, 10.9–not reached), with an overall response rate (ORR) of 20.5% (Figure 1). The disease control rate was 54.5%, the 1-year PFS-rate was 19.3% (95% CI, 10.1-37.2) and the median progression-free survival (PFS) was 2.8 months (95% CI, 1.8-7.4).
Translational research component
The study included a pre-planned biomarker study. Archived, paraffin-embedded NPC samples were successfully collected from 42 participants. Plasma samples were collected from 43 subjects. No statistical difference in OS or PFS was observed between patients considered PD-L1–negative (PD-L1 expression <1%; N=24) vs PD-L1–positive patients (PD-L1 expression ≥1%; N=18).
Six (33%) patients with PD-L1–positive NPC responded to nivolumab vs three (13%) patients with PD-L1–negative NPC (not significant). Previously, the group presented incomplete data in 21 patients during the American Association for Cancer Research (AACR) Annual Meeting 2017 summarising the response rates by PD-L1 expression (Table 1).
Do you like our content? Subscribe to our non-intrusive newsletter today! We promise we won’t be spammy.
YOU MAY ALSO LIKE
|PD-L1 Expression||Progression Disease (%)||Stable Disease (%)||Partial Response (%)|
|No PD-L1 expression||1||1||–|
|Less than 1%||6||2||–|
Forty-one samples could be stained for human leukocyte antigen (HLA) A and B expression, and the survival and response rates are reported in Table 2. There was a statistical difference in the 1-year PFS-rate and median PFS between NPC patients whose cancers showed loss of expression of HLA-A and/or HLA-B. The difference in the 1-year OS rate was non-significant, and the difference in median OS was not yet evaluable. Finally, the response rates did not show a statistical difference.
|Measurement||Subjects with loss of HLA-A and/or B expression||Subjects with HLA-A and B expression||Statistical Assessment|
|1-year PFS rate||30.9%||5.6%||Reached significance|
|Median PFS||4.8 months||1.8 months||Reached significance|
|1-year OS rate||75.7%||33.8%||Not significant|
|Median OS||Not reached||10.9 months||Not evaluable|
|Response rate||19.2%||22.2%||Not significant|
Most patients permanently discontinued treatment because of disease progression (69.2%). Approximately 10% of patients discontinued treatment because of toxicities.
Forty-five patients were evaluable for AEs. Most toxicities were according to the nivolumab US FDA approved package insert (USPI). Ten (22.2%) subjects experienced grade ≥3 AEs, including colitis, diarrhoea, fatigue, increase in aspartate transaminase (AST) or alanine aminotransferase levels (ALT), neutropenia, hyponatremia, and lymphopenia. During treatment, one patient died of pulmonary tuberculosis.
This article is not medical advice. Patients should seek personal assessment by a licenced specialist. Physicians are recommended to read the full publication(s) as cited in the article before making medical decisions. This article does not supersede nor replace the published article(s).
© Copyright 2018 MediPaper Medical Communications Ltd. – Immunotherapy & ImmunoOncology (I-O) Nivolumab NPC Opdivo Nasopharyngeal Carcinoma Brigette Ma CUHK Phase II NCI-9742 study JCO Journal of Clinical Oncology 2018