SCOTTSDALE, ARIZ. – Patients with head and neck cancer undergoing radiation therapy do not have better survival if given induction chemotherapy instead of concurrent chemotherapy, finds a cohort study reported at the Multidisciplinary Head and Neck Cancer Symposium.
Dr. Daniel W. Bowles
Using the National Cancer Data Base, Dr. Daniel W. Bowles and his colleagues analyzed outcomes for 8,003 patients treated for nonmetastatic but more advanced disease with one of these two approaches.
Results reported in a poster session and related press briefing showed that the patients given induction chemotherapy were more likely to receive radiation doses lower than those recommended in guidelines and lived, on average, about 13 months less.
“The use of induction chemotherapy is not supported by this analysis,” commented Dr. Bowles, director of cancer research at the University of Colorado at Denver, Aurora, and staff physician at the Denver VA Medical Center.
The study – the largest yet to compare the two approaches and specifically in a cohort of patients with more advanced disease – adds to others that have hinted at inferior outcomes with induction chemotherapy as compared with concurrent chemotherapy, the standard of care.
“Recently, there have been several randomized controlled studies that have looked at induction chemotherapy followed by concurrent chemoradiation versus concurrent chemoradiation alone,” he elaborated. “These studies have had somewhat varied results, but have been critiqued as being underpowered and [the possibility] that no survival benefit was seen in the induction chemotherapy arm perhaps because there were too many low-risk cancers that were included in these studies, including patients who have stage III cancer or patients who had N0 to N2a disease.”
Dr. Randall J. Kimple
Press briefing moderator Dr. Randall J. Kimple of the University of Wisconsin–Madison, commented, “I think this study adds to the growing data that I would say is now nearly overwhelming that induction chemotherapy, other than in maybe very selected cases, has essentially no role in the treatment of head and neck cancer patients in a routine setting and outside of the setting of a clinical trial.”
The investigators included in their analysis patients with stage Tis-T4,N2b-3,M0 squamous cell carcinoma of the oropharynx, hypopharynx, or larynx diagnosed between 2003 and 2011 and treated with external-beam radiation therapy, without surgery.
Analyses were based on 1,907 patients given induction chemotherapy (starting 43 to 98 days before radiation therapy) and 6,086 patients given concurrent chemotherapy (starting within 7 days of radiation therapy).
In univariate analyses, median overall survival was 52.1 months with induction chemotherapy versus 64.9 months with concurrent chemotherapy, reported Dr. Bowles, who disclosed that he had no relevant conflicts of interest. The difference translated to a 14% higher risk of death with the former (hazard ratio, 1.14; P less than .01).
In multivariate analysis, survival did not differ significantly between the two chemotherapy approaches in the cohort as a whole or in various subgroups of patients having especially advanced disease: those with T4 or N3 disease, with N3 disease only, or with T4N3 disease. Repeating analyses after propensity score matching yielded essentially the same results.
“We couldn’t identify any specific subgroups that appeared to benefit with regards to overall survival,” Dr. Bowles commented, while also noting some caveats.
“One potential limitation from looking at the National Cancer Data Base is that they only provide information about overall survival. We don’t know about cancer-specific survival, so you can’t say based on these data whether there is a progression-free survival benefit. The other question is how this affects quality of life,” he elaborated. “Those are important questions, [whether] induction chemotherapy would benefit anyone with regards to those outcomes. We just don’t have that data from the National Cancer Data Base.”
In other study findings, compared with peers given concurrent chemotherapy, patients given induction chemotherapy were more likely to receive a radiation dose less than the minimum of 66 Gy recommended by the National Comprehensive Cancer Network and the American Society for Radiation Oncology (20.9% vs. 14.9%, P less than .01).
In multivariate analyses, patients given induction chemotherapy were still less likely to receive guideline-concordant doses of radiation (odds ratio, 1.42; P less than .01), and receipt of such doses was associated with an increased risk of death (HR, 1.76; P less than .01).