Pembrolizumab alone or with chemotherapy for recurrent or metastatic head and neck squamous cell carcinoma: Health-related quality-of-life results from KEYNOTE-048.

OBJECTIVES: To assess health-related quality of life (HRQoL) with first-line pembrolizumab, pembrolizumab-chemotherapy, or cetuximab-chemotherapy in recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC) in the phase 3 KEYNOTE-048 trial (NCT02358031). MATERIALS AND METHODS: HRQoL was measured using the European Organisation for Research and Treatment of Cancer 30-question quality-of-life (EORTC QLQ-C30), the EORTC 35-question quality-of-life head and neck cancer-specific module (EORTC QLQ-H&N35), and the EuroQol 5-dimension 3-level instruments (EQ-5D-3L). Secondary endpoints included mean change from baseline in EORTC QLQ-C30 global health status/quality of life (GHS/QoL) at week 15 and time to deterioration (TTD) in EORTC QLQ-C30 GHS/QoL and EORTC QLQ-H&N35 pain and swallowing. RESULTS: Of 882 enrolled participants, 844 received ≥ 1 dose of study treatment and completed ≥ 1 HRQoL assessment; adherence was ≥ 79% at week 15 across treatment groups. At week 15, EORTC QLQ-C30 GHS/QoL scores remained stable; no clinically meaningful between-group differences were observed (least squares mean difference, pembrolizumab vs cetuximab-chemotherapy, 0.24; 95% CI, -3.34 to 3.82; pembrolizumab-chemotherapy vs cetuximab-chemotherapy, 0.40; 95% CI, -3.46 to 4.26). Median TTD in EORTC QLQ-C30 GHS/QoL and EORTC QLQ-H&N35 pain and swallowing scores was not reached over 51 weeks across groups, showing stable HRQoL. TTD was similar between groups for EORTC QLQ-C30 GHS/QoL (pembrolizumab vs cetuximab-chemotherapy: HR, 1.38; 95% CI, 0.95-2.00; pembrolizumab-chemotherapy vs cetuximab-chemotherapy: HR, 1.37; 95% CI, 0.94-2.00), as was TTD in EORTC QLQ-H&N35 pain and swallowing scores. CONCLUSIONS: Pembrolizumab monotherapy and pembrolizumab-chemotherapy extended OS while maintaining HRQoL, further supporting first-line use for R/M HNSCC.

Health-Related Quality of Life of Patients with Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma Treated with Pembrolizumab in KEYNOTE-629.

INTRODUCTION: Pembrolizumab provided durable responses and acceptable safety in recurrent or metastatic (R/M) cutaneous squamous cell carcinoma (cSCC) in the KEYNOTE-629 study. In this elderly, fragile population with disfiguring tumours, preservation of health-related quality of life (HRQoL) is critical. Here, we present pre-specified exploratory HRQoL analyses from the first interim analysis of KEYNOTE-629. METHODS: Patients with R/M cSCC not amenable to surgery or radiation therapy received pembrolizumab 200 mg every 3 weeks for ≤ 24 months. HRQoL end points included change from baseline to week 12 in European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Core 30 (EORTC QLQ-C30) global health status (GHS)/QoL, functioning, symptom and European Quality of Life 5-Dimension 5-Level (EQ-5D-5L) scores and change from baseline through week 48 in EORTC QLQ-C30 GHS/QoL and physical functioning scores. Improvement (≥ 10-point increase post-baseline with confirmation) was assessed using the exact binomial method. RESULTS: Analyses included 99 patients for EORTC QLQ-C30 and 100 for EQ-5D-5L. Compliance was > 80% at week 12. Mean scores were stable from baseline to week 12 for GHS/QoL (4.95 points; 95% confidence interval, -1.00 to 10.90) and physical functioning (-3.38 points; 95% confidence interval, -8.80 to 2.04). EORTC-QLQ-C30 functioning, symptom, and EQ-5D-5L scores remained stable at week 12. Post-baseline scores were improved in 29.3% of patients for GHS/QoL, 17.2% for physical functioning, and in a numerically higher proportion of responders versus non-responders (GHS/QoL, 55.6% versus 16.1%; physical functioning, 36.1% versus 7.1%). CONCLUSIONS: In elderly patients with R/M cSCC, the clinical efficacy of pembrolizumab translates into a benefit validated by HRQoL preservation or improvement during treatment. TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03284424.

Cutaneous squamous cell carcinoma (cSCC) is the second most common type of non-melanoma skin cancer. cSCC is usually caused by cumulative exposure to sunlight and often occurs in exposed parts of the body such as the head and neck. cSCC is most often seen in older people. If cSCC is detected early, it can be removed by surgery; however, if left untreated, the cancer can spread throughout the body and cause death. The disease itself and its treatment can be painful, cause scarring, or change the patient's physical appearance. Hence, people with cSCC often have poor quality of life. It is therefore important to develop new drugs to help patients with cSCC live longer without worsening their quality of life. The phase 2 KEYNOTE-629 study investigated how well the drug pembrolizumab treated cSCC and whether it was safe. KEYNOTE-629 included patients who were mostly older and had advanced cSCC. The results showed that pembrolizumab was effective and safe. Here, we investigated how pembrolizumab affected the quality of life of these patients. To do this, we asked patients to answer questionnaires on important aspects of their experience, such as their general health status, physical functioning, emotional wellbeing, and symptoms. We found that patients who were treated with pembrolizumab had stable quality of life during treatment. Furthermore, patients whose cancer responded well to pembrolizumab were more likely to have an improved quality of life. These results support the use of pembrolizumab in patients with advanced cSCC.