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Nivolumab demonstrates efficacy in recurrent, metastatic SCCHN
NEW ORLEANS — Treatment with nivolumab improved OS in patients with recurrent or metastatic squamous cell carcinoma of the head and neck refractory to platinum-based therapy, according to phase 3 study results presented at the American Association for Cancer Research Annual Meeting.
Nivolumab (Opdivo, Bristol-Myers Squibb) exhibited efficacy regardless of patients’ PD-L1 or HPV status, results showed.
Maura L. Gillison
“Nivolumab fulfills an incredible unmet need in the clinic,” Maura L. Gillison, MD, PhD, professor of internal medicine and Jeg Coughlin chair of cancer research at The Ohio State University Wexner Medical Center, said during a press conference. “Platinum-refractory head and neck cancer is an absolutely devastating disease. These patients have unbelievable functional problems with things we all take for granted — speech, chewing, communicating, breathing. Their disease rapidly progresses. This is the first time in my career that I’ve had an agent to reach for in this population.”
Patients with platinum-refractory recurrent or metastatic SCCHN have no further chemotherapeutic options for extending survival and often face poor prognosis, according to study background.
The anti–PD-L1 monoclonal antibody nivolumab is FDA–approved for the treatment of several tumor types, including melanoma and non–small cell lung cancer.
Gillison and colleagues conducted a randomized, open-label, phase 3 clinical trial of 361 patients (median age, 60 years; 76.4% current or former smokers; 54.8% previously treated with 2 or more prior chemotherapy lines) with HNSCC who progressed within 6 months of platinum-based chemotherapy.
Patients who received systemic therapy subsequent to biopsy or prior to screening were not eligible. Those assigned nivolumab could continue treatment beyond disease progression if there was evidence of clinical benefit.
The researchers randomly assigned patients to biweekly nivolumab (3 mg/kg; n = 240) or weekly investigator’s choice (IC; n = 121) of single-agent methotrexate (40-60 mg/m2 loading dose), docetaxel (30-40 mg/m2 loading dose) or cetuximab (Erbitux, Lilly; 400 mg/m2 loading dose).
Following the loading doses, patients assigned IC received a weekly dose of 250 mg/m2.
OS served as the primary endpoint. Secondary endpoints included PFS, objective response rate, safety, and outcomes defined by PD-L1 and HPV.
Patients assigned nivolumab had a median OS of 7.5 months (95% CI, 5.5-9.1), compared with 5.1 months (95% CI, 4-6) in the IC arm (P = .01). These data equated to a 30% reduction in risk for death with nivolumab (HR = 0.7; 97.73% CI, 0.51-0.96).
However, patients in the IC arm had a slightly longer median PFS (2.4 months vs. 2 months).
The overall response rate (ORR) in the nivolumab arm was 12.1% (95% CI, 8.2-16.9). There were six complete responses and 23 partial responses by RECIST criteria.
The ORR in the IC arm was 7.4% (95% CI, 3.5-13.7), with one complete response and eight partial responses.
Median duration of response had not been reached for nivolumab (95% CI, 5.5-not estimable) but was 3 months (95% CI, 0-4.8) for IC.
Seventy-two percent of patients (n = 260) had evaluable tumor PD-L1 status.
Patients with PD-L1 expression greater than or equal to 1% achieved a median OS of 8.7 months in the nivolumab arm and 4.6 months in the IC arm (HR = 0.55; 95% CI, 0.36-0.83). Among patients with PD-L1 expression of less than 1%, median OS was 5.7 months for nivolumab and 5.8 months for IC (HR = 0.89; 95% CI, 0.54-1.45).
The researchers had access to HPV data from 178 patients (49.3%).
HPV–positive patients achieved a median OS of 9.1 months on nivolumab and 4.4 months on IC (HR = 0.56; 95% CI, 0.32-0.99). For HPV–negative patients, median OS was 7.5 months with nivolumab and 5.8 months with IC (HR = 0.73; 95% CI, 0.42-1.25).
Treatment-related adverse events of any grade occurred in 58.9% of patients assigned nivolumab and 77.5% of patients assigned IC. Grade 3 or higher adverse events occurred in 13.1% of patients assigned nivolumab and 35.1% of patients assigned IC.
The most commonly reported adverse events included fatigue (nivolumab, 14%; IC, 17.1%), nausea (nivolumab, 8.5%; IC, 20.7%), diarrhea (nivolumab, 6.8%; IC, 13.5%) and anemia (nivolumab, 5.1%; IC, 16.2%).
The researchers reported three treatment-related deaths (nivolumab, n = 2; IC, n = 1).
“The important part of these data is that they provide a new therapeutic option for this patient population,” Gillison said. “Head and neck cancer was not previously considered to be a reasonable disease target for immunotherapy. The nivolumab data are already serving as a platform for combination therapies with other immunotherapies.” – by Cameron Kelsall
Reference:
Gillison ML, et al. Abstract CT099. Presented at: American Association for Cancer Research Annual Meeting; April 16-20, 2016; New Orleans.
Disclosure: Bristol-Myers Squibb funded the study. Gillison reports funding from the Oral Cancer Foundation during the conduct of this study, as well as consultant roles with Bristol-Myers Squib, Eli Lilly and Merck.
Perspective
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This is the first randomized phase 3 trial of immunotherapy in squamous cell carcinoma of the head and neck to be reported. It showed an OS improvement with the use of a PD-1 inhibitor, and I expect that we will see the use of nivolumab (Opdivo, Bristol-Myers Squibb) in this setting.
In order to put these data in perspective and to help us better understand how to use these drugs, we need to see response rate and PFS data.
There was a clear difference of benefit for nivolumab in patients expressing PD-L1 of at least 1% compared with those who did not. There were a significant number of patients for whom there was no PD-L1 status data, and it would be key to see if that was balanced across the arms.
Another issue is the use of investigator’s choice vs. nivolumab. Investigator’s choice could be methotrexate, docetaxel or cetuximab (Erbitux, Lilly) — three drugs with different response rates in this setting. We should see the breakdown by investigator’s choice. That might explain the surprisingly short median survival by patients with p16–positive disease assigned to investigator’s choice, which was shorter than patients with p16–negative disease — something we don’t normally see.
The data on pembrolizumab (Keytruda, Merck) in patients with head and neck cancer — presented last year at the ASCO and ESMO meetings — showed a 25% response rate and demonstrated the efficacy of PD-1 inhibitors in this patient population. However, the randomized data on pembrolizumab have not been reported yet.