Adding docetaxel to radiation therapy (RT) improved survival outcomes in cisplatin-ineligible patients with locally advanced head and neck squamous cell carcinoma, a phase III randomized trial showed.

At a median follow-up of 32.4 months, the 2-year disease-free survival (DFS) rate was 42% with docetaxel plus RT and 30.3% with RT alone (HR 0.673, 95% CI 0.521-0.868, P=0.002), reported Kumar Prabhash, MBBS, MD, DM, of Tata Memorial Hospital, Homi Bhabha National Institute in Mumbai, India, and colleagues.

Median overall survival (OS) was 25.5 months in the docetaxel arm and 15.3 months in the RT-alone arm (P=0.035), while the 2-year OS rates were 50.8% versus 41.7%, respectively (HR 0.747, 95% CI 0.569-0.980, P=0.035), they noted in the Journal of Clinical Oncology.

“To the best of our knowledge, this is the first randomized study demonstrating the benefit of an alternate radiosensitizing agent in cisplatin-ineligible patients with [locally advanced head and neck squamous cell carcinoma] in whom chemoradiation is indicated,” Prabhash and team wrote.

In explaining the rationale behind the study, the authors said that while cisplatin-based chemoradiation is the recommended regimen for locally advanced head and neck squamous cell carcinoma by all international guidelines, “it is not uncommon in routine clinical practice to encounter cisplatin-ineligible patients.” Moreover, there are limited data on systemic therapy options in cisplatin-ineligible patients, they added.

In an editorial accompanying the study, Loren K. Mell, MD, of the University of California San Diego, and Stuart J. Wong, MD, of the Medical College of Wisconsin in Milwaukee, noted that “it is high time to shift the conversation from whether radiosensitizers are beneficial, to which regimen (if any) provides the most benefit and should define the standard of care.”

While RT plus cetuximab (Erbitux) has been a standard regimen in the cisplatin-ineligible population, particularly in the U.S., the cost of cetuximab can be a barrier to utilization in low- and middle-income countries, “which bears consideration particularly if outcomes are equivalent, or nearly so, with less expensive agents,” they wrote.

Furthermore, while carboplatin plus fluorouracil have been shown to be effective in randomized trials, this combination is infrequently used in the U.S. because of toxicity concerns, they noted.

“On shooting down RT alone, docetaxel belongs in the armamentarium of go-to regimens, but since it was not compared head-to-head against prevailing alternatives, it should not be declared the lone standard,” Mell and Wong suggested, adding that randomized trials are needed to see whether any non-cisplatin regimen prevails.

For this study, conducted from July 2017 to May 2021, 356 patients with nonmetastatic, locally advanced head and neck squamous cell carcinoma warranting chemoradiation were randomized 1:1 to RT alone (median age 63, 85% men) or RT with concurrent docetaxel 15 mg/m² once weekly for a maximum of seven cycles (median age 61, 81.8% men). All patients had an Eastern Cooperative Oncology Group performance status of 0-2.

In regard to adverse events (AEs), docetaxel increased acute grade ≥3 AEs overall compared with RT alone (82% vs 58%), and resulted in a higher incidence of grade ≥3 mucositis (49.7% vs 22.2%), odynophagia (52.5% vs 33.5%), and dysphagia (49.7% vs 33%). The risk of aspiration pneumonia, although low overall, was also higher with docetaxel (7% vs 2%), while febrile neutropenia from docetaxel was very low (0.6%).

“The addition of any systemic therapy to radiation is known to increase AEs,” Prabhash and colleagues wrote. “However, in our study, these complications were manageable and did not affect the compliance with radiation. In view of clinically and statistically meaningful improvement in survival and manageable AEs, the increase in AEs should not be a deterrent for the use of docetaxel in cisplatin-ineligible patients.”

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