NEW YORK — Treatment of recurrent or metastatic head and neck cancer is challenging given the availability of only a few treatment options, according to a presenter at HemOnc Today New York.
Results of the randomized EXTREME study — published a decade ago — established a clear standard of care for first-line treatment of recurrent disease, Robert Haddad, MD, disease center leader of the head and neck oncology program at Dana-Farber Cancer Institute, said during his presentation. That regimen consists of the EGFR inhibitor cetuximab (Erbitux, Eli Lilly) plus 5-FU and either cisplatin or carboplatin.
That regimen “unfortunately” remains the standard of care for those patients, Haddad said.
“Checkpoint inhibitors are active in the recurrent metastatic setting, and now we have two PD-1 inhibitors approved for second-line treatment,” Haddad said. “Even though we have newer treatment options, we still need to look for more therapies for these patients.”
Several factors guide treatment selection for recurrent/metastatic head and neck cancer. They include performance status, comorbidities, prior treatment, symptoms, patient preference and logistics, and biomarkers.
“As you are faced with a patient with recurrent head and neck cancer, the first question we try to answer is, is this patient still curable?” Haddad said. “When the patient is not curable, we look at palliative systemic treatments.”
Historically, first-line treatment included platinum-based doublet. This conferred an overall response rate of 30% to 40%, and median survival was 6 months to 9 months regardless of treatment.
Clinical trials showed combination regimens increased response rates compared with single agents but did not improve survival.
The EXTREME trial — published in 2008 in The New England Journal of Medicine — evaluated the addition of cetuximab to 5-FU with either cisplatin or carboplatin. Treatment in both groups continued until progression or toxicity.
Results showed the cetuximab regimen prolonged median OS (10.1 months vs. 7.4 months; HR = 0.79; 95% CI, 0.64-0.98).
Use of targeted therapy for second-line treatment of recurrent or metastatic head and neck cancer has been “a very challenging field,” Haddad said.
Aside from cetuximab, EGFR inhibitors have not demonstrated clinically meaningful efficacy in head and neck cancer.
A randomized phase 3 trial evaluated platinum-based chemotherapy with or without bevacizumab (Avastin, Genentech) for 403 patients with recurrent or metastatic squamous cell carcinoma of the head and neck. Treatment continued every 21 days until progression.
OS served as the primary endpoint.
Results, presented at last year’s ASCO Annual Meeting, showed the bevacizumab regimen did not lead to a statistically significant improvement in median OS (12.6 months vs. 11 months; HR = 0.84; 95% CI, 0.67-1.05).
“Remember, with the EXTREME trial, patients treated with chemotherapy only had OS of 7.4 months,” Haddad said. “Now we’re seeing 11 months with chemotherapy, even though it’s the same patient population, so maybe things are getting better over time.”
Two checkpoint inhibitors, nivolumab (Opdivo, Bristol-Myers Squibb) and pembrolizumab (Keytruda, Merck), are approved for second-line treatment of recurrent or metastatic disease; however, they also have shown benefit for patients within 6 months of definitive treatment.
PD-L1 positive patients fare better with these drugs than those who are PD-L1 negative, and that is consistent across all immunotherapy trials in head and neck cancer so far, Haddad said.
“The PD-L1 marker appears to be quite relevant in this disease,” Haddad said. “You’re not required to check PD-L1 status ... but data from the trials tell us if you’re not PD-L1 positive, you might be at a disadvantage in terms of response and survival to these drugs.” – by Mark Leiser
Haddad R. Head and neck cancer: Current state of treatment of recurrent/metastatic disease. Presented at: HemOnc Today New York; March 8-10, 2018; New York.
Haddad reports research funding from AstraZeneca, Bristol-Myers Squibb, Celgene, Genentech, Merck and Pfizer, and consultant roles with AstraZeneca, Bristol-Myers Squibb, Eisai, Genentech, Merck and Pfizer. He also is a member of National Comprehensive Cancer Network’s head and neck committee, as well as chair of its thyroid committee.