Nivolumab for NPC: immunotherapy active in nasopharyngeal carcinoma (NCI-9742)

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IMMUNOTHERAPY

NIVOLUMAB FOR NPC: IMMUNOTHERAPY ACTIVE IN NASOPHARYNGEAL CARCINOMA (NCI-9742)

Medical writer: Stijn van den Borne, MSc | On: 31st March 2018 | In: Head and Neck Cancer, ImmunoOncology, Immunotherapy, Oncology

Article Keywords

BMS, Bristol-Myers Squibb, Nasopharyngeal Carcinoma, nasopharynx, nivolumab, NPC, Oncology News, Opdivo, PD-1

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

Key Results

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).

PD-L1 expression

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).

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**Table 1.** Response rates by PD-L1 expression (partial data) in 21 participants of the NCI-9742 study with nivolumab in nasopharyngeal carcinoma (NPC) as presented during the AACR Annual Meeting 2017
PD-L1 Expression	Progression Disease (%)	Stable Disease (%)	Partial Response (%)
No PD-L1 expression	1	1	–
Less than 1%	6	2	–
5%	–	4	2
10%	1	–	–
20%	–	1	–
30%	–	1	1
80%	–	–	1

HLA expression

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.

**Table 2.** Survival and responses in patients with loss of HLA-A and/or B expression vs patients with HLA-A and B expression in the NCI-9742 study of nivolumab in nasopharyngeal carcinoma (NPC)
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

Adverse events

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.

Citations

Ma BBY et al. J Clin Oncol. Published online March 27, 2018. doi: 10.1200/JCO.2017.77.0388.

Ma BBY et al. Cancer Res 2017;77(13 Suppl):Abstract nr CT076. doi: 10.1158/1538-7445.AM2017-CT076.

Disclaimer

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

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