Maura L. Gillison
Nivolumab immunotherapy appeared safe and feasible to administer in conjunction with radiation and chemotherapy for patients with newly diagnosed local-regionally advanced squamous cell carcinoma of the head and neck, according to results from the RTOG Foundation 3504 trial scheduled for presentation at the Multidisciplinary Head and Neck Cancers Symposium.
“Patients with mouth and throat cancer ... often present with advanced disease and relapse within 2 years,” Maura L. Gillison, MD, PhD, professor of thoracic/head and neck medical oncology at The University of Texas MD Anderson Cancer Center, said during a press conference. “We’ve previously shown that PD-1 checkpoint receptor nivolumab [Opdivo, Bristol-Myers Squibb] improves survival for patients whose cancer has progressed after platinum chemotherapy. That result suggests that incorporating these drugs earlier in the initial therapy of [patients with head and neck cancer] has tremendous potential to improve their survival and prevent those relapses.”
Gillison and colleagues studied 20 patients (median age, 56 years; 70% men; 85% Caucasian) with newly diagnosed intermediate- or high-risk HNSCC to see if nivolumab could be given as part of first-line treatment with weekly or high-dose cisplatin chemoradiation. Most patients had advanced stages of disease (80% T3 or T4; 45% N2 or N3) and 55% had more than 10 pack-years of smoking history.
Eight patients in the weekly cisplatin group and nine in the high-dose cisplatin group were available for analysis.
All patients completed radiation therapy and 15 of 17 patients received 70% of their prescribed dose of platinum chemotherapy. Two patients discontinued therapy due to an allergic reaction and for cholecystitis.
Most patients started and completed nivolumab therapy. In the weekly cisplatin group, five of eight patients received 10 doses of concurrent nivolumab and two patients received nine doses. In the high-dose cisplatin group, five of nine patients received seven doses and three patients received six doses.
Among the first eight patients enrolled in the trial, six continued nivolumab for a year.
The trial design dictated only the first eight be evaluated for nivolumab treatment for a year, although more patients continued to receive nivolumab treatment.
No patients experienced grade 3 or higher nivolumab-related adverse events not resolved within 4 weeks or radiation therapy delays of more than 2 weeks. Researchers reported one case of anaphylaxis and one case of cholecystitis in the weekly cisplatin arm, although these were not attributed to nivolumab.
Grade 3 side effects related to nivolumab in the weekly arm included leukopenia (n = 2), as well as lymphopenia, fatigue, loss of appetite, lipase elevation, mucositis and adrenal insufficiency (n = 1 for each). In the high-dose arm, grade 3 side effects included diarrhea, lipase elevation and amylase elevation (n = 1 for each).
“The addition of nivolumab to standard-of-care cisplatin and radiation therapy was shown to be feasible and no new safety concerns were identified,” Gillison said during the press conference. “Importantly, standard-of-care therapy was not compromised by the addition of nivolumab. These patients undergo pretty intense therapy as part of standard of care and many of them are quite taxed by the therapy, so we were pleased to see that of the first eight patients who had the opportunity, six of them could tolerate that additional year of nivolumab therapy.”
Studies assessing the safety of nivolumab added to other chemotherapy platforms are ongoing, in addition to a randomized phase 3 study of concurrent nivolumab. – by Cassie Homer
Gillison M, et al. Abstract 2. Presented at Multidisciplinary Head and Neck Cancers Symposium; Feb. 15-17, 2018; Scottsdale, Ariz.
Disclosures: Gillison reports consultant roles with Bristol-Myers Squibb and Merck. Please see the abstract for a list of all other authors’ relevant financial disclosures.