For patients with locally advanced head and neck squamous cell carcinoma who cannot tolerate platinum chemotherapy, docetaxel is a sound alternative to enhance sensitivity to radiotherapy, say researchers reporting a phase 3 trial from India.
“This is the first randomized study demonstrating the benefit of an alternate radiosensitizing agent in cisplatin-ineligible patients,” they point out.
“We found that the use of docetaxel as a radiosensitizer in cisplatin-ineligible patients,” when compared to the use of radiation alone, “led to an improvement in disease-free survival, locoregional control, and overall survival without affecting the quality of life of the patients,” the team reports.
The investigators, led by Vijay Maruti Patil, MD, DM, a medical oncologist at Tata Memorial Hospital, Mumbai, noted that they stopped the trial early after the benefit from adding docetaxel became clear.
Cisplatin is the general standard of care to sensitize locally advanced head and neck tumors to radiation treatment, but up to a third of patients are ineligible because of age, diminished kidney function, hearing loss, and other problems, they point out.
Many alternatives to cisplatin are used in such settings, but until now, there hasn’t been any level 1, phase 3 evidence to guide the selection.
Cetuximab is the alternative used most often in the United States, but evidence supporting it was generated in trials involving cisplatin-eligible patients, the investigators point out. There is also a high incidence of skin and other toxicities and, in some studies, non-ideal survival outcomes, they note.
The new study was published online on December 9 in the Journal of Clinical Oncology.
It “demonstrates what could be presumed but was not known to be true in the cisplatin-ineligible context: Radiosensitizers improve outcomes over radiotherapy alone,” comment the authors of an accompanying editorial.
“Docetaxel belongs in the armamentarium of go-to regimens,” they declare. The authors are radiation oncologist Loren Mell, MD, of the University of California, San Diego, and medical oncologist Stuart Wong, MD, of the Medical College of Wisconsin, Milwaukee.
This study “fills an important gap in the head and neck cancer literature, but “since [docetaxel] was not compared head-to-head against” other radiosensitizing alternatives, it “should not be declared the lone standard…. 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,” they add.
Study Details
The trial randomly assigned 356 cisplatin-ineligible adults equally to either radiation alone or radiation with concurrent docetaxel 15 mg/m2 once weekly for a maximum of seven cycles. Investigators planned to enroll 600 patients but stopped the trial early when the survival benefit with docetaxel became clear.
The addition of docetaxel improved 2-year disease-free survival (42% vs 30.3%; hazard ratio [HR], 0.673; P = .002); 2-year overall survival (50.8% vs 41.7%; HR, 0.747; P = .035), and the 2-year locoregional failure rate (41.8% vs 54.7%; HR, 0.661; P = .002).
Median overall survival was 25.5 months with docetaxel, vs 15.3 months with radiation alone (P = .035).
Docetaxel’s benefits were most pronounced in patients with hypopharyngeal primary sites and among the 61% of patients treated definitively. There was “possibly” a benefit in the adjuvant setting, but “further study would be required to show definitive applicability,” the investigators say.
There was a higher incidence of grade ≥3 mucositis (49.7% vs 22.2%), odynophagia (52.5% vs 33.5%), and dysphagia (33%), but the “complications were manageable and did not affect the compliance” with either radiation or docetaxel, the team reports. Overall, 86% of patients received five or more cycles docetaxel.
In their editorial, Mell and Wong note that the “majority of patients did not receive intensity-modulated radiotherapy, the standard in higher-income countries,” but add that “we do not expect the use of conventional radiotherapy would reduce the effectiveness of docetaxel.”
The trial was funded by Tata Memorial Hospital, where it was conducted. Several investigators had industry ties, including Patil, who reported research funding from Johnson & Johnson/Janssen, AstraZeneca, Intas, NATCO Pharma, Eisai Germany, and Novartis. Mell is an advisor for Cel-Sci and reported research funding from Merck and AstraZeneca. Wong disclosed research funding from Novartis and Merck.
J Clin Oncol. Published online December 9, 2022. Abstract, Editorial
M. Alexander Otto is a physician assistant with a master’s degree in medical science and a journalism degree from Newhouse. He is an award-winning medical journalist who worked for several major news outlets before joining Medscape. Alex is also an MIT Knight Science Journalism fellow. Email: aotto@mdedge.com.
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