Patient-reported outcomes in immunotherapy for head and neck cancer
Corresponding Author
Kedar Kirtane MD
Department of Head and Neck-Endocrine Oncology, Moffitt Cancer Center, Tampa, Florida, USA
Correspondence
Kedar Kirtane, Department of Head and Neck-Endocrine Oncology, Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL 33612, USA.
Email: [email protected]
Search for more papers by this authorAasha I. Hoogland PhD
Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, Florida, USA
Search for more papers by this authorXiaoyin Li PhD
Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, Florida, USA
Search for more papers by this authorYvelise Rodriguez MS
Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, Florida, USA
Search for more papers by this authorKelsey Scheel BS
Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, Florida, USA
Search for more papers by this authorBrent J. Small PhD
School of Aging Studies, University of South Florida, Tampa, Florida, USA
Search for more papers by this authorLaura B. Oswald PhD
Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, Florida, USA
Search for more papers by this authorJameel Muzaffar MD
Department of Head and Neck-Endocrine Oncology, Moffitt Cancer Center, Tampa, Florida, USA
Search for more papers by this authorJulie A. Kish MD
Department of Personalized Medicine, Moffitt Cancer Center, Tampa, Florida, USA
Search for more papers by this authorMarcelo Bonomi MD
Department of Internal Medicine and The James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA
Search for more papers by this authorPriyanka Bhateja MD
Department of Internal Medicine and The James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA
Search for more papers by this authorNabil F. Saba MD
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA
Search for more papers by this authorConor E. Steuer MD
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA
Search for more papers by this authorChristine H. Chung MD
Department of Head and Neck-Endocrine Oncology, Moffitt Cancer Center, Tampa, Florida, USA
Search for more papers by this authorHeather S. L. Jim PhD
Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, Florida, USA
Search for more papers by this authorCorresponding Author
Kedar Kirtane MD
Department of Head and Neck-Endocrine Oncology, Moffitt Cancer Center, Tampa, Florida, USA
Correspondence
Kedar Kirtane, Department of Head and Neck-Endocrine Oncology, Moffitt Cancer Center, 12902 USF Magnolia Drive, Tampa, FL 33612, USA.
Email: [email protected]
Search for more papers by this authorAasha I. Hoogland PhD
Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, Florida, USA
Search for more papers by this authorXiaoyin Li PhD
Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, Florida, USA
Search for more papers by this authorYvelise Rodriguez MS
Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, Florida, USA
Search for more papers by this authorKelsey Scheel BS
Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, Florida, USA
Search for more papers by this authorBrent J. Small PhD
School of Aging Studies, University of South Florida, Tampa, Florida, USA
Search for more papers by this authorLaura B. Oswald PhD
Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, Florida, USA
Search for more papers by this authorJameel Muzaffar MD
Department of Head and Neck-Endocrine Oncology, Moffitt Cancer Center, Tampa, Florida, USA
Search for more papers by this authorJulie A. Kish MD
Department of Personalized Medicine, Moffitt Cancer Center, Tampa, Florida, USA
Search for more papers by this authorMarcelo Bonomi MD
Department of Internal Medicine and The James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA
Search for more papers by this authorPriyanka Bhateja MD
Department of Internal Medicine and The James Comprehensive Cancer Center, The Ohio State University, Columbus, Ohio, USA
Search for more papers by this authorNabil F. Saba MD
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA
Search for more papers by this authorConor E. Steuer MD
Department of Hematology and Medical Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia, USA
Search for more papers by this authorChristine H. Chung MD
Department of Head and Neck-Endocrine Oncology, Moffitt Cancer Center, Tampa, Florida, USA
Search for more papers by this authorHeather S. L. Jim PhD
Department of Health Outcomes and Behavior, Moffitt Cancer Center, Tampa, Florida, USA
Search for more papers by this authorAbstract
Background
Data about patient-reported outcomes (PROs) among patients with head and neck squamous cell carcinoma (HNSCC) treated with immune checkpoint inhibitors are sparse. Our exploratory study evaluated PROs in patients with HNSCC starting treatment with immune checkpoint inhibitor monotherapy or combination therapy with cetuximab.
Methods
Patients were recruited prior to receipt of their first checkpoint inhibitor therapy infusion. Participants completed measures of checkpoint inhibitor toxicities and quality of life (QOL) at on-treatment clinic visits.
Results
Among patients treated with checkpoint inhibitor monotherapy (n = 48) or combination therapy (n = 38) toxicity increased over time (p < 0.05), while overall QOL improved from baseline to 12 weeks, with stable or declining QOL thereafter (p < 0.05). There were no group differences in change in toxicity index or QOL. Toxicity index scores were significantly higher in the combination group at 18–20 weeks and 6 months post-initiation of immune checkpoint inhibitor (p < 0.05). There were no significant group differences at baseline, the 6–8 week (p = 0.13) or 3-month (p = 0.09) evaluations. The combination group reported better emotional well-being at baseline than the monotherapy group (p = 0.04), There were no other group differences QOL at baseline or later timepoints.
Conclusions
Despite increasing patient-reported toxicity, checkpoint inhibitor monotherapy and combination therapy were associated with similar transient improvements, then worsening, of QOL in patients with HNSCC.
Open Research
DATA AVAILABILITY STATEMENT
The data that support the findings of this study are available from the corresponding author upon reasonable request.
REFERENCES
- 1Ribas A. Tumor immunotherapy directed at PD-1. New Engl J Med. 2012; 366(26): 2517-2519.
- 2Sznol M, Longo DL. Release the hounds! Activating the t-cell response to cancer. New Engl J Med. 2015; 372(4): 374-375.
- 3Ferris RL, Blumenschein G Jr, Fayette J, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. New Engl J Med. 2016; 375(19): 1856-1867.
- 4Cohen EE, Harrington KJ, Le Tourneau C, et al. Pembrolizumab (pembro) vs standard of care (SOC) for recurrent or metastatic head and neck squamous cell carcinoma (R/M HNSCC): phase 3 KEYNOTE-040 trial. Ann Oncol. 2017; 28:v628.
- 5Burtness B, Harrington KJ, Greil R, et al. Pembrolizumab alone or with chemotherapy versus cetuximab with chemotherapy for recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-048): a randomised, open-label, phase 3 study. Lancet. 2019; 394(10212): 1915-1928.
- 6Chung CH, Bonomi M, Steuer CE, et al. Concurrent cetuximab and nivolumab as a second-line or beyond treatment of patients with recurrent and/or metastatic head and neck squamous cell carcinoma: results of phase I/II study. Cancer. 2021; 13(5):1180.
- 7Rodriguez CP, Wu QV, Voutsinas J, et al. A phase II trial of pembrolizumab and vorinostat in recurrent metastatic head and neck squamous cell carcinomas and salivary gland cancer. Clin Cancer Res. 2020; 26(4): 837-845.
- 8Siu LL, Even C, Mesia R, et al. Safety and efficacy of durvalumab with or without tremelimumab in patients with PD-L1-low/negative recurrent or metastatic HNSCC: the phase 2 CONDOR randomized clinical trial. JAMA Oncol. 2019; 5(2): 195-203.
- 9Sacco AG, Chen R, Worden FP, et al. Pembrolizumab plus cetuximab in patients with recurrent or metastatic head and neck squamous cell carcinoma: an open-label, multi-arm, non-randomised, multicentre, phase 2 trial. Lancet Oncol. 2021; 22(6): 883-892.
- 10Saba NF, Steuer CE, Ekpenyong A, et al. Pembrolizumab and cabozantinib in recurrent metastatic head and neck squamous cell carcinoma: a phase 2 trial. Nat Med. 2023; 29: 880-887.
- 11Chung CH, Li J, Steuer CE, et al. Phase II multi-institutional clinical trial result of concurrent cetuximab and nivolumab in recurrent and/or metastatic head and neck squamous cell carcinoma. Clin Cancer Res. 2022; 28(11): 2329-2338.
- 12Michot JM, Bigenwald C, Champiat S, et al. Immune-related adverse events with immune checkpoint blockade: a comprehensive review. Eur J Cancer. 2016; 54: 139-148.
- 13Garon EB, Rizvi NA, Hui R, et al. Pembrolizumab for the treatment of non-small-cell lung cancer. New Engl J Med. 2015; 372(21): 2018-2028.
- 14Herbst RS, Baas P, Kim DW, et al. Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2016; 387(10027): 1540-1550.
- 15Robert C, Schachter J, Long GV, et al. Pembrolizumab versus ipilimumab in advanced melanoma. New Engl J Med. 2015; 372(26): 2521-2532.
- 16Patrick DL, Burke LB, Powers JH, et al. Patient-reported outcomes to support medical product labeling claims: FDA perspective. Value Health. 2007; 10: S125-S137.
- 17Kluetz PG, Slagle A, Papadopoulos EJ, et al. Focusing on core patient-reported outcomes in cancer clinical trials: symptomatic adverse events, physical function, and disease-related symptoms. Clin Cancer Res. 2016; 22(7): 1553-1558.
- 18Di Maio M, Basch E, Bryce J, Perrone F. Patient-reported outcomes in the evaluation of toxicity of anticancer treatments. Nat Rev Clin Oncol. 2016; 13(5): 319-325.
- 19Basch E, Abernethy AP, Mullins CD, et al. Recommendations for incorporating patient-reported outcomes into clinical comparative effectiveness research in adult oncology. J Clin Oncol. 2012; 30(34): 4249-4255.
- 20Pietanza MC, Basch EM, Lash A, et al. Harnessing technology to improve clinical trials: study of real-time informatics to collect data, toxicities, image response assessments, and patient-reported outcomes in a phase II clinical trial. J Clin Oncol. 2013; 31(16): 2004-2009.
- 21Atkinson TM, Li Y, Coffey CW, et al. Reliability of adverse symptom event reporting by clinicians. Qual Life Res. 2012; 21(7): 1159-1164.
- 22Fromme EK, Eilers KM, Mori M, Hsieh Y-C, Beer TM. How accurate is clinician reporting of chemotherapy adverse effects? A comparison with patient-reported symptoms from the quality-of-life questionnaire C30. J Clin Oncol. 2004; 22(17): 3485-3490.
- 23Falchook AD, Green R, Knowles ME, et al. Comparison of patient- and practitioner-reported toxic effects associated with chemoradiotherapy for head and neck cancer. JAMA Otolaryngol Head Neck Surg. 2016; 142(6): 517-523.
- 24Di Maio M, Gallo C, Leighl NB, et al. Symptomatic toxicities experienced during anticancer treatment: agreement between patient and physician reporting in three randomized trials. J Clin Oncol. 2015; 33(8): 910-915.
- 25Kam D, Salib A, Gorgy G, et al. Incidence of suicide in patients with head and neck cancer. JAMA Otolaryngol Head Neck Surg. 2015; 141(12): 1075-1081.
- 26Gonzalez BD, Eisel SL, Bowles KE, et al. Meta-analysis of quality of life in cancer patients treated with immune checkpoint inhibitors. J Natl Cancer Inst. 2022; 114(6): 808-818.
- 27Harrington KJ, Ferris RL, Blumenschein G Jr, et al. Nivolumab versus standard, single-agent therapy of investigator's choice in recurrent or metastatic squamous cell carcinoma of the head and neck (CheckMate 141): health-related quality-of-life results from a randomised, phase 3 trial. Lancet Oncol. 2017; 18(8): 1104-1115.
- 28Hansen AR, Ala-Leppilampi K, McKillop C, et al. Development of the functional assessment of cancer therapy-immune checkpoint modulator (FACT-ICM): a toxicity subscale to measure quality of life in patients with cancer who are treated with ICMs. Cancer. 2020; 126(7): 1550-1558.
- 29Langlais B, Mazza GL, Thanarajasingam G, et al. Evaluating treatment tolerability using the toxicity index with patient-reported outcomes data. J Pain Symptom Manage. 2022; 63(2): 311-320.
- 30Rogatko A, Babb JS, Wang H, Slifker MJ, Hudes GR. Patient characteristics compete with dose as predictors of acute treatment toxicity in early phase clinical trials. Clin Cancer Res. 2004; 10(14): 4645-4651.
- 31List MA, D'Antonio LL, Cella DF, et al. The performance status scale for head and neck cancer patients and the functional assessment of cancer therapy-head and neck scale. A study of utility and validity. Cancer. 1996; 77(11): 2294-2301.
10.1002/(SICI)1097-0142(19960601)77:11<2294::AID-CNCR17>3.0.CO;2-S CAS PubMed Web of Science® Google Scholar
- 32Norman GR, Sloan JA, Wyrwich KW. Interpretation of changes in health-related quality of life: the remarkable universality of half a standard deviation. Med Care. 2003; 41(5): 582-592.
- 33Laugsand EA, Sprangers MA, Bjordal K, Skorpen F, Kaasa S, Klepstad P. Health care providers underestimate symptom intensities of cancer patients: a multicenter European study. Health Qual Life Outcomes. 2010; 8:104.
- 34Bulls HW, Chang PH, Brownstein NC, et al. Patient-reported symptom burden in routine oncology care: examining racial and ethnic disparities. Cancer Rep (Hoboken). 2022; 5(3):e1478.
