Of the 16 treatment options compared and ranked, HFCRT topped the list for overall survival, event-free survival, locoregional control, and cancer-specific death.
The results also suggested that taxane-based induction chemotherapy followed by locoregional therapy, especially with concomitant chemotherapy, “is another good option in selected patients with a good performance status and minor comorbidities,” according to investigator Claire Petit, MD, PhD, of Centre hospitalier de l’Université de Montréal in Canada, and colleagues.
The investigators concluded that further intensifying chemoradiotherapy with these approaches “could improve outcomes over chemoradiotherapy.”
The findings, published in The Lancet Oncology, “could help to guide clinical decision-making in locally advanced head and neck cancer with a high risk of locoregional failure, especially human papillomavirus–negative tumours,” the authors wrote.
However, Jared Weiss, MD, of the University of North Carolina, Chapel Hill, cautioned that this “study is an individual patient data network meta-analysis, not a randomized controlled trial. As the authors note, it can help frame existing data but cannot define standard of care.”
Still, “it does support the efficacy of two commonly considered intensification strategies for high-risk patients – hyperfractionation of the radiation and the addition of preceding induction chemotherapy. Both of these intensifications substantially increase the time commitment from the patient, and many patients find this unacceptable. But, for select patients, hyperfractionation and induction chemotherapy have a role and may be considered for patients at high risk of treatment failure,” Dr. Weiss said.
Study details
The goal of this study was to find the best option among many chemoradiation approaches for head and neck cancer. The investigators pulled together and reanalyzed individual patient data from recently updated meta-analyses.
The current analysis included 115 randomized trials that enrolled patients between Jan. 1, 1980, and April 30, 2012. This encompassed 28,978 patients with 20,579 progression events and 19,253 deaths over a median follow-up of 6.6 years.
Treatments were ranked by P score, with higher scores indicating more effective therapies.
For overall survival, HFCRT had a P score of 97%. The hazard ratio (HR) was 0.63 for the comparison with locoregional therapy alone (surgery, radiotherapy, or both). The absolute benefit at 5 years, compared with locoregional therapy alone, was 16.7% with HFCRT.
The P score for the second most effective treatment option – induction chemotherapy with taxane, cisplatin, and fluorouracil followed by locoregional therapy (ICTaxPF-LRT) – was 89%, with a hazard ratio of 0.69 and an absolute benefit at 5 years of 13.4%, versus locoregional therapy.
The HR of HFCRT versus the accepted standard of care worldwide – locoregional therapy with concomitant platinum-based chemotherapy and radiotherapy (CLRTP) – was 0.82 in favor of HFCRT for overall survival and 0.80 for event-free survival.
For overall survival, the P score for CLRTP was 78%. Three other treatment options had a better P score than CLRTP but not a better HR (0.77). These included ICTaxPF-LRT (P score, 89%; HR, 0.69), accelerated radiotherapy with concomitant chemotherapy (P score, 82%; HR, 0.75), and ICTaxPF-LRT followed by CLRTP (P score, 80%; HR, 0.75).
In the end, the investigators found “superiority of HFCRT over other treatments,” but noted it can be difficult to implement HFCRT in the era of intensity-modulated radiotherapy for head and neck cancer. Even so, HFCRT “could be considered as an option for tertiary centres with a high throughput of patients,” the investigators wrote.
The team noted that one of the limitations of this study is that cancer care has improved substantially since the very earliest trials that were included in the analysis. This introduces potential confounders, including that patients in older trials might have been understaged so that even an experimental local therapy would have been less effective.
Toxicity wasn’t part of this analysis but must be taken into account when making therapeutic decisions, “especially because HFCRT and induction chemotherapy based on taxane, cisplatin, and fluorouracil are known to be toxic,” the investigators wrote.
This research was funded by the French Institut National du Cancer, French Ligue Nationale Contre le Cancer, and Fondation ARC. The authors disclosed relationships with numerous companies, including AbbVie, Lilly, and Merck. Dr. Weiss did not report any relevant conflicts.