SCOTTSDALE, Ariz.—The role of induction chemotherapy remains controversial in locally advanced head and neck squamous cell carcinoma (HNSCC). The failure to demonstrate an overall survival benefit over concurrent chemoradiation in clinical trials may stem from the studies' lack of power due to slow accrual, or from the inclusion of patients with less-advanced nodal disease.
On the other hand, it may have less to do with statistical power or patient selection and more to do with difficulty in completing guideline-concordant care following induction chemotherapy.
An analysis of the National Cancer Data Base by researchers from the University of Colorado School of Medicine showed that in HNSCC patients with advanced nodal disease, induction chemotherapy patients were more likely to receive less-than-definitive doses of radiotherapy.
The analysis also showed that overall survival with induction chemotherapy was not significantly different from that of concurrent chemoradiation patients, even in subgroup analyses of increasingly advanced disease.
“Head and neck cancer patients who receive induction chemotherapy rather than the standard treatment of concurrent chemoradiation do not benefit from increased survival rates and are less likely to receive a full course of radiation,” said Daniel W. Bowles, MD, an Assistant Professor in the Department of Medical Oncology at the University of Colorado School of Medicine and Director of Cancer Research and staff physician at the Denver VA Medical Center, a co-author of the study.
Bowles presented the data here at the 2016 Head & Neck Multidisciplinary Symposium, sponsored by the American Society for Radiation Oncology (ASTRO) and the American Society of Clinical Oncology (ASCO).
The study analyzed data from 8,003 patient records in the National Cancer Data Base of patients diagnosed with T(any) N2b-3 M0 oropharyngeal, laryngeal, and hypopharyngeal cancers between 2003 and 2011. The Database is a jointly-sponsored project of the American College of Surgeons and the American Cancer Society.
Bowles said most randomized trials designed to address whether induction chemotherapy improves outcomes by enhancing local control and minimizing distant metastases have been based on study designs that enrolled too few patients or too few patients with advanced cancers, thereby diluting the possible benefit of induction therapy.
In this analysis, cases were classified into two cohorts based on the type of treatment delivered. Patients in the induction chemotherapy group (1,917) began chemotherapy in 43 to 98 days prior to radiation therapy. This time frame allowed for two to three cycles of induction chemotherapy, which is the common protocol in recent clinical trials, Bowles said.
Patients in the concurrent chemoradiation group (6,086) began chemotherapy within seven days of radiotherapy start and did not receive induction chemotherapy.
Bowles said the induction-therapy group tended to be younger than the concurrent-radiation patients. They presented with more advanced T stage and N stage, and with more oropharynx primary disease.
Less-Than-Full Radiotherapy Course
Importantly, the induction chemotherapy patients were less likely to receive a full course of radiotherapy following administration of induction chemotherapy.
Bowles reported 21 percent of the induction chemotherapy patients received less-than-definitive doses of radiotherapy, that is, less than the 66 Gy in the National Comprehensive Cancer Network and ASTRO guidelines, compared with 15 percent of the chemoradiotherapy patients.
Multivariate analyses adjusting for age, sex, race, income, location, year, comorbidities, primary disease site, T-status, and N-status confirmed the increased odds among the induction cohort of receiving non-guideline-concordant radiotherapy doses.
Comparative analysis also indicated a slightly shorter median survival following induction chemotherapy compared to chemoradiotherapy, with a median overall survival of 52 months for induction chemotherapy patients versus 65 months for chemoradiotherapy, but this difference did not persist on multivariate or propensity score matched analysis, Bowles added.
Subgroup analyses further divided the treatment cohorts by disease stage to assess possible benefits of induction chemotherapy for advanced cases of HNSCC.
Induction chemotherapy did not improve overall survival even for patients with the most advanced disease, including T4, N3, or T4N3 status.
Potential Study Limitations
Bowles said one potential limitation in using the National Cancer Data Base is that it provides only survival data and not cancer-specific survival.
“So based on these data it is not possible to say there is a progression-free survival benefit to induction chemotherapy,” he said.
The database also does not describe quality of life, he said.
In a statement released before the meeting, Bowles said that while the researchers suspected that induction chemotherapy would not have an impact on our entire study population, they thought it might prolong survival for the most advanced cancers.
“Our finding from this large database that induction chemotherapy is not associated with improved overall survival over chemoradiation, even for these patients, will continue to dampen enthusiasm for routine use of induction therapy,” Bowles said. “In cancer care, sometimes more is less. If adding induction chemotherapy fails to improve survival over the current standard of care, then we should reconsider its use.”
Essentially No Role
This study was described for the press in an online preview before the symposium.
The moderator of the preview, Randall Kimple, MD, Assistant Professor in the Department of Human Oncology, University of Wisconsin School of Medicine and Public Health, Madison, said this study adds to the growing data—“nearly overwhelming”—that induction chemotherapy has essentially no role in the treatment of head and neck cancer patients except in very select cases or in a clinical trial.
He added, though, that the study “shows there is essentially no benefit to induction chemotherapy—it doesn't say it is worse, just that it is not better.”
In an interview with OT after the meeting, Kimple said induction chemotherapy in HNSCC is used in approximately 10 percent of cases, and tends to be institution specific.
“Some groups use it a lot and some never use it outside of a trial protocol,” Kimple said.
Robert H. Carlson is a contributing writer.