Nick Mulcahy

February 19, 2016

Every once in a while, a medical expert throws caution to the wind and announces that a scientific presentation has shut the door on a clinical question — with a bang.

Such appeared to be the case today during a presscast from the 2016 Multidisciplinary Head and Neck Cancer Symposium in Scottsdale, Arizona.

The study that inspired the door slamming was a retrospective analysis of patients with advanced head and neck cancer comparing induction chemotherapy (IC), administered prior to radiation therapy, with the standard treatment of concurrent chemoradiation (CRT).

Study coauthor Daniel W. Bowles, MD, a medical oncologist at the University of Colorado, Denver, explained why the analysis was undertaken.

IC is an "intensification strategy," said Dr Bowles, "that theoretically has many benefits, such as decreasing distant metastatic rates, providing tumor debulking, and potentially improving overall survival."

Recently, there have been several randomized controlled trials that compared the strategy of IC followed by CRT with CRT alone, he noted.

But the trials have had problems, said Dr Bowles. Underpowered designs and too many lower-risk cancers might explain the lack of overall survival benefit that has been repeatedly seen with the more intensive IC strategy.

So Dr Bowles and his colleagues decided to examine whether IC improves survival in patients with advanced head and neck squamous cell carcinoma. They identified 8003 patients diagnosed with T(any) N2b–3 M0 oropharyngeal, laryngeal, or hypopharyngeal cancers from 2003 to 2011 in the National Cancer Data Base.

All the patients received chemotherapy and radiation therapy, but the timing indicated whether it was IC (chemo 43 to 98 days before radiation) or CRT (chemo within 7 days of radiation).

IC resulted in inferior overall survival, according to unadjusted results.

Specifically, median overall survival was better in the 6086 patients treated with CRT than in the 1907 treated with IC (64.9 vs 52.1 months; P < .01).

Additionally, more patients treated with IC than with CRT failed to reach the desired radiation treatment dose threshold of 66 Gy (20.9% vs 14.9%).

The IC patients, overall, were younger, had more oropharynx primaries, and had higher tumor and nodal stages.

These differences necessitated multivariate analysis, which showed that there was no statistically significant difference in overall survival between IC and CRT (hazard ratio [HR], 1.04; P = .28).

In the same analysis, when the researchers compared patients with the highest burdens of disease (T4 or N3), the overall survival benefit was no better with IC than with CRT (HR, 0.99; P = .81).

This finding is especially disappointing, said Dr Bowles.

"While we suspected that induction chemotherapy would not have an impact on our entire study population, we thought it might prolong survival for the most advanced cancers," he noted in a press statement.

Dr Bowles then suggested that IC should not be used regularly.

"Our finding from this large database that IC is not associated with improved overall survival over CRT, even for these patients, will continue to dampen enthusiasm for routine use of induction therapy. In cancer care, sometimes more is less," he said.

The "use of induction chemotherapy is not supported by this analysis," Dr Bowles concluded at the presscast.

But a more dramatic statement was made by Randall Kimple, MD, from the University of Wisconsin – Madison, who moderated the presscast.

Induction chemotherapy, other than in maybe very select cases, has essentially no role in treatment of head and neck cancer patients.

This study "adds to the growing data, which I would say is now nearly overwhelming, that induction chemotherapy, other than in maybe very select cases, has essentially no role in the treatment of head and neck cancer patients in a routine setting."

But although Dr Kimple shut the door on the question of using IC in head and neck cancer, he added a caveat: there might be clinical trials involving IC that will be exceptions to this rule.

In endorsing standard CRT in this setting, Dr Kimple also stressed that CRT "is curative for a large portion of our head and neck cancer patients."

Finally, in this study, no subgroups benefited from IC. "We couldn't identify any subgroups that appeared to receive an overall survival benefit,"Dr Bowles added.

Dr Bowles has disclosed no relevant financial relationships. Dr Kimble is a consultant to Cancer CarePoint.

2016 Multidisciplinary Head and Neck Cancer Symposium (MHNCS): Abstract 109. Presented February 18, 2016.


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