In the Journals

Nivolumab improves quality of life for advanced head and neck cancer

Nivolumab led to greater stabilization of symptoms and functioning among patients with recurrent or metastatic head and neck squamous cell carcinoma than investigator’s choice of therapy, according to results of a quality-of-life analysis from the CheckMate 141 clinical trial.

Patients treated with nivolumab (Opdivo, Bristol-Myers Squibb) also experienced better quality of life for longer.

Kevin J. Harrington

“When immunotherapies first hit the clinic, there were concerns over side effects and the fact that they didn’t work for everyone, but in only 2 or 3 years, we have become very good at managing the side effects they cause and we are better able to select patients in whom these treatments are most likely to be effective,” Kevin J. Harrington, MD, PhD, professor in biological cancer therapies at The Institute of Cancer Research in London and a consultant clinical oncologist at The Royal Marsden NHS Foundation Trust in London, said in a press release.

Researchers randomly assigned 361 patients with platinum-refractory recurrent or metastatic HNSCC to receive 3 mg/kg nivolumab via IV infusion biweekly or investigator’s choice of methotrexate (40-60 mg/kg/m2), docetaxel (30-40 mg/kg/m2) or cetuximab (Erbitux, Eli Lilly; 250 mg/kg/m2), until disease progression, intolerable toxicity or withdrawal.

Previously reported data from the trial showed nivolumab significantly extended survival compared with single-agent chemotherapy in this population.

In the current analysis, Harrington and colleagues evaluated quality-of-life data from the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (QLQ-30) and Head and Neck Cancer module, and the 3-level EQ-5D questionnaire, which patients completed at baseline, 9 weeks and then every 6 weeks thereafter during treatment.

The change from baseline analysis included 129 patients (nivolumab, n = 93; investigator’s choice, n = 36) who completed any of the questionnaires at baseline and at least one other assessment.

By week 15 patients in the nivolumab arm demonstrated mean changes ranging from –2.1 to 5.4 across function and symptom domains on the QLQ-30 assessment. None of these changes showed clinically meaningful deterioration, whereas eight of the fifteen domains (53%) did in the chemotherapy arm (range in change, –24.5 to 2.4).

On the head and neck module, clinically meaningful worsening occurred for no domains among patients in the nivolumab arm but eight of eight domains (44%) in the chemotherapy arm.

Further, on the EQ-5D questionnaire, patients in the nivolumab arm demonstrated clinically meaningful improvement, whereas patients in the chemotherapy arm demonstrated clinically meaningful deterioration (7.3 vs. –7.8).

At weeks 9 and 15, patients in the nivolumab arm showed significantly and clinically meaningful differences in role functioning, social functioning, fatigue, dyspnea and appetite loss on the QLQ-30 and pain and sensory problems on the head and neck module.

Patients on the nivolumab arm demonstrated significantly longer median time to deterioration on 13 of 35 domains (37%) across the three assessments.

“Head and neck cancer is an extremely debilitating disease and if it spreads or patients relapse then it’s extremely difficult to treat,” Harrington said. “But our research has found that nivolumab really is a game-changing treatment for patients with head and neck cancer.

“We now need to test if we can move away from resorting to traditional chemotherapies, which come with far too much collateral damage, and see these smarter, kinder therapies used as a first-line treatment to replace chemotherapy altogether,” Harrington added.

The measurement and analysis of quality of life in clinical trials may be challenging and present limitations, Susanne Singer, PhD, MSc, professor in the division of epidemiology and health services research at Institute of Medical Biostatistics, Epidemiology and Informatics at University Medical Centre Mainz in Germany, wrote in a related editorial.

The Checkmate 141 trial had multiple limitations, Singer wrote, including that it was an open-label trial which could have influenced patient-reported outcomes; patients with worse quality of life at baseline became lost to follow-up sooner than patients treated longer; and the exploratory analysis meant a lack of hypotheses.

Despite these, the results offer a clear look into patient-reported outcomes with this treatment.

“Bearing these limitations in mind, Checkmate 141 offers valuable insight into the potential effects of nivolumab on certain quality-of-life domains in patients with advanced head and neck cancer who are reasonably fit,” Singer wrote. – by Melinda Stevens

Disclosure: Harrington reports consultant roles with AstraZeneca, Bristol-Myers Squibb, Merck, Merck Sharp & Dohme and Pfizer. Please see the full study for a list of all other researchers’ relevant financial disclosures. Singer reports a grant from Pfizer; the quality of life prize from Eli Lilly; travel grants from Genzyme; and lecture fees from AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb and Pfizer.

Nivolumab led to greater stabilization of symptoms and functioning among patients with recurrent or metastatic head and neck squamous cell carcinoma than investigator’s choice of therapy, according to results of a quality-of-life analysis from the CheckMate 141 clinical trial.

Patients treated with nivolumab (Opdivo, Bristol-Myers Squibb) also experienced better quality of life for longer.

Kevin J. Harrington

“When immunotherapies first hit the clinic, there were concerns over side effects and the fact that they didn’t work for everyone, but in only 2 or 3 years, we have become very good at managing the side effects they cause and we are better able to select patients in whom these treatments are most likely to be effective,” Kevin J. Harrington, MD, PhD, professor in biological cancer therapies at The Institute of Cancer Research in London and a consultant clinical oncologist at The Royal Marsden NHS Foundation Trust in London, said in a press release.

Researchers randomly assigned 361 patients with platinum-refractory recurrent or metastatic HNSCC to receive 3 mg/kg nivolumab via IV infusion biweekly or investigator’s choice of methotrexate (40-60 mg/kg/m2), docetaxel (30-40 mg/kg/m2) or cetuximab (Erbitux, Eli Lilly; 250 mg/kg/m2), until disease progression, intolerable toxicity or withdrawal.

Previously reported data from the trial showed nivolumab significantly extended survival compared with single-agent chemotherapy in this population.

In the current analysis, Harrington and colleagues evaluated quality-of-life data from the European Organization for Research and Treatment of Cancer Quality-of-Life Questionnaire (QLQ-30) and Head and Neck Cancer module, and the 3-level EQ-5D questionnaire, which patients completed at baseline, 9 weeks and then every 6 weeks thereafter during treatment.

The change from baseline analysis included 129 patients (nivolumab, n = 93; investigator’s choice, n = 36) who completed any of the questionnaires at baseline and at least one other assessment.

By week 15 patients in the nivolumab arm demonstrated mean changes ranging from –2.1 to 5.4 across function and symptom domains on the QLQ-30 assessment. None of these changes showed clinically meaningful deterioration, whereas eight of the fifteen domains (53%) did in the chemotherapy arm (range in change, –24.5 to 2.4).

On the head and neck module, clinically meaningful worsening occurred for no domains among patients in the nivolumab arm but eight of eight domains (44%) in the chemotherapy arm.

Further, on the EQ-5D questionnaire, patients in the nivolumab arm demonstrated clinically meaningful improvement, whereas patients in the chemotherapy arm demonstrated clinically meaningful deterioration (7.3 vs. –7.8).

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At weeks 9 and 15, patients in the nivolumab arm showed significantly and clinically meaningful differences in role functioning, social functioning, fatigue, dyspnea and appetite loss on the QLQ-30 and pain and sensory problems on the head and neck module.

Patients on the nivolumab arm demonstrated significantly longer median time to deterioration on 13 of 35 domains (37%) across the three assessments.

“Head and neck cancer is an extremely debilitating disease and if it spreads or patients relapse then it’s extremely difficult to treat,” Harrington said. “But our research has found that nivolumab really is a game-changing treatment for patients with head and neck cancer.

“We now need to test if we can move away from resorting to traditional chemotherapies, which come with far too much collateral damage, and see these smarter, kinder therapies used as a first-line treatment to replace chemotherapy altogether,” Harrington added.

The measurement and analysis of quality of life in clinical trials may be challenging and present limitations, Susanne Singer, PhD, MSc, professor in the division of epidemiology and health services research at Institute of Medical Biostatistics, Epidemiology and Informatics at University Medical Centre Mainz in Germany, wrote in a related editorial.

The Checkmate 141 trial had multiple limitations, Singer wrote, including that it was an open-label trial which could have influenced patient-reported outcomes; patients with worse quality of life at baseline became lost to follow-up sooner than patients treated longer; and the exploratory analysis meant a lack of hypotheses.

Despite these, the results offer a clear look into patient-reported outcomes with this treatment.

“Bearing these limitations in mind, Checkmate 141 offers valuable insight into the potential effects of nivolumab on certain quality-of-life domains in patients with advanced head and neck cancer who are reasonably fit,” Singer wrote. – by Melinda Stevens

Disclosure: Harrington reports consultant roles with AstraZeneca, Bristol-Myers Squibb, Merck, Merck Sharp & Dohme and Pfizer. Please see the full study for a list of all other researchers’ relevant financial disclosures. Singer reports a grant from Pfizer; the quality of life prize from Eli Lilly; travel grants from Genzyme; and lecture fees from AstraZeneca, Boehringer-Ingelheim, Bristol-Myers Squibb and Pfizer.