Induction Chemo Offers No OS Benefit for Locally Advanced Head and Neck Cancer

Daniel W. Bowles, MD

The use of induction chemotherapy for advanced head and neck squamous cell carcinoma (HNSCC) does not improve overall survival (OS), according to an analysis of over 8000 patient records from the National Cancer Database (NCDB).

No improvement in OS was found for induction chemotherapy versus concurrent chemotherapy plus radiation, according to multivariant analysis (HR, 1.04; 95% CI, 0.97-1.13; P = .28). Similarly, patients with the worst cancers, T4 or N3 disease, did not benefit from induction chemotherapy compared with concurrent chemotherapy plus radiation, according to multivariant analysis (HR, 0.99; 95% CI, 0.89-1.10; P = .81).

“Most importantly, we found no OS difference between those receiving induction chemotherapy and those receiving concurrent chemoradiation,” study co-author Daniel W. Bowles, MD, an assistant professor in the department of Medical Oncology at the University of Colorado School of Medicine, said in a presscast at the 2016 Multidisciplinary Head and Neck Cancer Symposium.

“Looking exclusively at patients who had the worst of the worst cancers, those with T4 or N3 disease, again, we have no difference in OS [HR, 0.99].”

Bowles and colleagues examined data from NCDB records of 8003 patients with Tis-T4, N2b-3, M0 squamous cell carcinomas of the oropharynx, larynx, and hypopharynx from 2003 to 2011. Those with cancer of the oral cavity were excluded.

Induction chemotherapy was defined as chemotherapy administered 43 to 98 days before radiation therapy, and concurrent chemotherapy plus radiation was defined as chemotherapy occurring within 7 days of radiation therapy and not receiving induction chemotherapy. Among the study population, 1917 patients received induction chemotherapy and 6086 received concurrent chemoradiation.

The median OS was 52 months for patients who received induction chemotherapy and 65 months for patients who received concurrent chemoradiation therapy (P <.01 by comparative analysis using Cox regression), though this difference did not persist on multivariate (HR for mortality, 1.04; P = .28) or propensity score-matched analysis (P = .18).

Induction chemotherapy occurred more in patients who were younger (P <.01), had more oropharynx primaries (P <.01), had higher T stage (P <.01), and had higher N stage (P <.01). Yet, induction chemotherapy did not improve OS for these patients. Even for patients with the most advanced disease, induction chemotherapy did not improve OS, including T4 or N3 status (HR, 0.99; P =.81), N3 status (HR, 0.98; P = .84), and T4N3 status (HR, 0.91; P = .53).

Bowles stated that no subgroups of patients appeared to benefit from induction chemotherapy.

Less than a full dose of radiation therapy (<66 Gy) was received by 21% of the patients who received induction chemotherapy and 15% of the patients who received concurrent chemoradiation (P <.01). According to multivariant analysis that adjusted for age, sex, race, income, location, year, comorbidities, primary disease site, T-status, and N-status, patients who received induction chemotherapy had increased odds of receiving less than 66 Gy of radiation therapy, which is not concordant with guidelines (OR, 1.42; 95% CI, 1,25-1.63). Receiving less than 66 Gy was associated with worsened OS (HR, 1.76 by multivariant analysis; 95% CI, 1.65-1.89; P <.01).

“Radiation dose remains an important overall risk factor for OS, with patients receiving guideline-consistent radiation having better OS,” said Bowles. He explained that NCCN guidelines call for ≥66 Gy of radiation therapy.

“Looking at the data in a slightly different way, with propensity score matching on Kaplan Meier curves, again, no difference in OS between the 2 groups,” said Bowles, in showing Kaplan-Meier curves comparing induction chemotherapy and concurrent chemotherapy plus radiation (HR, 1.07; 95% CI, 0.97-1.18; P = .18). Similar results were found when the treatments were compared for patients with oropharynx (HR, 1.25; 95% CI, 1.13-1.39; P <.01), hypopharynx (HR, 1.21; 95% CI, 0.98-1.50; P = .08) and larynx (HR, 0.96; 95% CI, 0.83-1.11; P = .56) cancer.

“Induction chemotherapy was associated with a lower overall dose of radiation therapy. Independent of these things, radiation therapy of less than 66 Gy was associated with lowered OS. The use of induction chemotherapy is not supported by these analyses,” concluded Bowles.

Stokes W, Amini A, McDermott J, et al. Induction chemotherapy predicts cumulative radiation dose and fails to improve survival in advanced head and neck cancer, a National Cancer Database analysis. Presented at: 2016 Multidisciplinary Head and Neck Cancer Symposium; February 18-20, 2016; Scottsdale, AZ. Abstract 109.

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