Effectiveness and safety of nivolumab in patients with head and neck cancer in Japanese real-world clinical practice: a multicenter retrospective clinical study

Nobuhiro Hanai, Yasushi Shimizu, Shin Kariya, Ryuji Yasumatsu, Tomoya Yokota, Takashi Fujii, Kiyoaki Tsukahara, Masafumi Yoshida, Kenji Hanyu, Tsutomu Ueda, Hitoshi Hirakawa, Shunji Takahashi, Takeharu Ono, Daisuke Sano, Moriyasu Yamauchi, Akihito Watanabe, Koichi Omori, Tomoko Yamazaki, Nobuya Monden, Naomi Kudo, Makoto Arai, Daiju Sakurai, Takahiro Asakage, Issei Doi, Takayuki Yamada, Akihiro Homma, Nobuhiro Hanai, Yasushi Shimizu, Shin Kariya, Ryuji Yasumatsu, Tomoya Yokota, Takashi Fujii, Kiyoaki Tsukahara, Masafumi Yoshida, Kenji Hanyu, Tsutomu Ueda, Hitoshi Hirakawa, Shunji Takahashi, Takeharu Ono, Daisuke Sano, Moriyasu Yamauchi, Akihito Watanabe, Koichi Omori, Tomoko Yamazaki, Nobuya Monden, Naomi Kudo, Makoto Arai, Daiju Sakurai, Takahiro Asakage, Issei Doi, Takayuki Yamada, Akihiro Homma

Abstract

Background: To fill the data gap between clinical trials and real-world settings, this study assessed the overall effectiveness and safety of nivolumab in patients with head and neck cancer (HNC) during Japanese real-world clinical practice.

Methods: This was a multicenter, retrospective study in Japanese patients with recurrent or metastatic HNC who received nivolumab for the first time between July and December 2017. Data on the clinical use, effectiveness, and safety of nivolumab were extracted from patient medical records.

Results: Overall, 256 patients were enrolled in this study. The median duration of nivolumab treatment was 72.5 days, with patients receiving a median of 6.0 (range 1-27) doses. Median overall survival (OS) was 9.5 (95% confidence interval [CI] 8.2-12.0) months and the estimated 12-month OS rate was 43.2%. The objective response rate (ORR) was 15.7% overall and 21.1%, 7.1%, and 13.6% in patients with primary nasopharynx, maxillary sinus, and salivary gland tumors, respectively, who had been excluded from CheckMate 141. Grade ≥ 3 immune-related adverse events occurred in 5.9% of patients. No new safety signals were identified compared with adverse events noted in CheckMate 141.

Conclusions: The effectiveness and safety of nivolumab in real-world clinical practice are consistent with data from the CheckMate 141 clinical trial. Therapeutic response was also observed in the groups of patients excluded from CheckMate 141.

Trial registration number: UMIN-CTR (UMIN000032600), Clinicaltrials.gov (NCT03569436).

Keywords: Multicenter retrospective study; Nivolumab; Real-world clinical practice; Recurrent or metastatic head and neck cancer.

Conflict of interest statement

N. Hanai, Y. Shimizu, S. Kariya, R. Yasumatsu, T. Fujii, M. Yoshida, K. Hanyu, H. Hirakawa, T. Ono, D. Sano, M. Yamauchi, K. Omori, N. Kudo, M. Arai, D. Sakurai, T. Asakage, A. Homma, T. Yokota, K. Tsukahara, S. Takahashi, and T. Yamazaki report grants from Bristol-Myers Squibb K.K. and Ono Pharmaceutical during the conduct of the study; K. Tsukahara, and S. Takahashi report personal fees from Bristol-Myers Squibb K.K. and Ono Pharmaceutical during the conduct of the study; T. Ueda reports grants from Ono Pharmaceutical; A. Watanabe, and N. Monden report nothing to disclose during the conduct of the study; I. Doi is an employee of Ono Pharmaceutical; T. Yamada is an employee of Bristol-Myers Squibb.

Figures

Fig. 1
Fig. 1
a Overall response rate b progression-free survival and c overall survival among all patients. CI confidence intervals, BOR best overall response, CR complete response, ORR objective response rate, OS overall survival, PD progressive disease, PFS progression-free survival, PR partial response, SD stable disease
Fig. 2
Fig. 2
a Overall response rate b progression-free survival and c overall survival among patients stratified according to the primary site. BOR best overall response, CR complete response, NR not reached, ORR objective response rate, OS overall survival, PD progressive disease, PFS progression-free survival, PR partial response, SD stable disease. *Primary tumor types excluded from Checkmate 141 study
Fig. 3
Fig. 3
a Overall response rate b progression-free survival and c overall survival among patients stratified according to platinum-sensitive or platinum-refractory status. BOR best overall response, CR complete response, ORR objective response rate, OS overall survival, PD progressive disease, PFS progression-free survival, PR partial response, SD stable disease. *Log-rank test
Fig. 4
Fig. 4
a Overall response rate b progression-free survival and c overall survival among patients according to ECOG status. BOR best overall response, CR complete response, ECOG PS Eastern Cooperative Oncology Group performance status, NR not reached, ORR objective response rate, OS overall survival, PD progressive disease, PFS progression-free survival, PR partial response, SD stable disease. *Log-rank test
Fig. 5
Fig. 5
a Progression-free survival and b overall survival according to the best overall response at 3 months. CR complete response, OS overall survival, PD progressive disease, PFS progression-free survival, PR partial response, SD stable disease. *Log-rank test

References

    1. Ferris RL, Blumenschein G, Jr, Fayette J, et al. Nivolumab for recurrent squamous-cell carcinoma of the head and neck. N Engl J Med. 2016;375(19):1856–1867. doi: 10.1056/NEJMoa1602252.
    1. Ferris RL, Blumenschein G, Jr, Fayette J, et al. Nivolumab vs investigator's choice in recurrent or metastatic squamous cell carcinoma of the head and neck: 2-year long-term survival update of CheckMate 141 with analyses by tumor PD-L1 expression. Oral Oncol. 2018;81:45–51. doi: 10.1016/j.oraloncology.2018.04.008.
    1. Kim ES, Bruinooge SS, Roberts S, et al. Broadening eligibility criteria to make clinical trials more representative: American Society of Clinical Oncology and Friends of Cancer Research Joint Research Statement. J Clin Oncol. 2017;35(33):3737–3744. doi: 10.1200/JCO.2017.73.7916.
    1. Antonia SJ, Borghaei H, Ramalingam SS, et al. Four-year survival with nivolumab in patients with previously treated advanced non-small-cell lung cancer: a pooled analysis. Lancet Oncol. 2019;20(10):1395–1408. doi: 10.1016/S1470-2045(19)30407-3.
    1. Yamazaki N, Kiyohara Y, Uhara H, et al. Long-term follow up of nivolumab in previously untreated Japanese patients with advanced or recurrent malignant melanoma. Cancer Sci. 2019;110(6):1995–2003. doi: 10.1111/cas.14015.
    1. Eisenhauer EA, Therasse P, Bogaerts J, et al. New response evaluation criteria in solid tumours: revised RECIST guideline (version 1.1) Eur J Cancer. 2009;45(2):228–247. doi: 10.1016/j.ejca.2008.10.026.
    1. Hori R, Shinohara S, Kojima T, et al. Real-world outcomes and prognostic factors in patients receiving nivolumab therapy for recurrent or metastatic head and neck carcinoma. Cancers (Basel) 2019;11(9):1317. doi: 10.3390/cancers11091317.
    1. Okamoto I, Sato H, Kondo T, et al. Efficacy and safety of nivolumab in 100 patients with recurrent or metastatic head and neck cancer—a retrospective multicentre study. Acta Otolaryngol. 2019;139(10):918–925. doi: 10.1080/00016489.2019.1648867.
    1. Cohen EEW, Soulieres D, Le Tourneau C, et al. Pembrolizumab versus methotrexate, docetaxel, or cetuximab for recurrent or metastatic head-and-neck squamous cell carcinoma (KEYNOTE-040): a randomised, open-label, phase 3 study. Lancet. 2019;393(10167):156–167. doi: 10.1016/S0140-6736(18)31999-8.
    1. Vermorken JB, Mesia R, Rivera F, et al. Platinum-based chemotherapy plus cetuximab in head and neck cancer. N Engl J Med. 2008;359(11):1116–1127. doi: 10.1056/NEJMoa0802656.
    1. Burtness 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. doi: 10.1016/S0140-6736(19)32591-7.
    1. Borcoman E, Kanjanapan Y, Champiat S, et al. Novel patterns of response under immunotherapy. Ann Oncol. 2019;30(3):385–396. doi: 10.1093/annonc/mdz003.
    1. Ma BBY, Lim WT, Goh BC, et al. Antitumor activity of nivolumab in recurrent and metastatic nasopharyngeal carcinoma: an international, multicenter study of the Mayo Clinic Phase 2 Consortium (NCI-9742) J Clin Oncol. 2018;36(14):1412–1418. doi: 10.1200/JCO.2017.77.0388.
    1. Ma Y, Fang W, Zhang Y, et al. A phase I/II open-label study of nivolumab in previously treated advanced or recurrent nasopharyngeal carcinoma and other solid tumors. Oncologist. 2019;24(7):891–e431. doi: 10.1634/theoncologist.2019-0284.
    1. Rodriguez 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. 2019;26:837–845. doi: 10.1158/1078-0432.CCR-19-2214.
    1. Cooper JS, Porter K, Mallin K, et al. National Cancer Database report on cancer of the head and neck: 10-year update. Head Neck. 2009;31(6):748–758. doi: 10.1002/hed.21022.
    1. Schneider K, Marbaix E, Bouzin C, et al. Immune cell infiltration in head and neck squamous cell carcinoma and patient outcome: a retrospective study. Acta Oncol. 2018;57(9):1165–1172. doi: 10.1080/0284186X.2018.1445287.
    1. Talani C, Makitie A, Beran M, et al. Early mortality after diagnosis of cancer of the head and neck: a population-based nationwide study. PLoS ONE. 2019;14(10):e0223154. doi: 10.1371/journal.pone.0223154.
    1. Japanese Society of Clinical Oncology . New clinical oncology. 4. Tokyo: Nankodo; 2015.
    1. Depenni R, Cossu Rocca M, Ferrari D, et al. Clinical outcomes and prognostic factors in recurrent and/or metastatic head and neck cancer patients treated with chemotherapy plus cetuximab as first-line therapy in a real-world setting. Eur J Cancer. 2019;115:4–12. doi: 10.1016/j.ejca.2019.03.022.
    1. Morita R, Okishio K, Shimizu J, et al. Real-world effectiveness and safety of nivolumab in patients with non-small cell lung cancer: a multicenter retrospective observational study in Japan. Lung Cancer. 2020;140:8–18. doi: 10.1016/j.lungcan.2019.11.014.
    1. Nakamura Y, Kitano S, Takahashi A, et al. Nivolumab for advanced melanoma: pretreatment prognostic factors and early outcome markers during therapy. Oncotarget. 2016;7(47):77404–77415. doi: 10.18632/oncotarget.12677.
    1. Nishikawa D, Suzuki H, Koide Y, et al. Prognostic markers in head and neck cancer patients treated with nivolumab. Cancers (Basel) 2018;10(12):466. doi: 10.3390/cancers10120466.
    1. Cowey CL, Liu FX, Black-Shinn J, et al. Pembrolizumab utilization and outcomes for advanced melanoma in US community oncology practices. J Immunother. 2018;41(2):86–95. doi: 10.1097/CJI.0000000000000204.
    1. Liu FX, Ou W, Diede SJ, et al. Real-world experience with pembrolizumab in patients with advanced melanoma: a large retrospective observational study. Medicine (Baltimore) 2019;98(30):e16542. doi: 10.1097/MD.0000000000016542.
    1. Sternberg CN, Loriot Y, James N, et al. Primary results from SAUL, a multinational single-arm safety study of atezolizumab therapy for locally advanced or metastatic urothelial or nonurothelial carcinoma of the urinary tract. Eur Urol. 2019;76(1):73–81. doi: 10.1016/j.eururo.2019.03.015.
    1. Aspeslagh S, Matias M, Palomar V, et al. In the immuno-oncology era, is anti-PD-1 or anti-PD-L1 immunotherapy modifying the sensitivity to conventional cancer therapies? Eur J Cancer. 2017;87:65–74. doi: 10.1016/j.ejca.2017.09.027.
    1. Saleh K, Daste A, Martin N, et al. Response to salvage chemotherapy after progression on immune checkpoint inhibitors in patients with recurrent and/or metastatic squamous cell carcinoma of the head and neck. Eur J Cancer. 2019;121:123–129. doi: 10.1016/j.ejca.2019.08.026.
    1. Schvartsman G, Peng SA, Bis G, et al. Response rates to single-agent chemotherapy after exposure to immune checkpoint inhibitors in advanced non-small-cell lung cancer. Lung Cancer. 2017;112:90–95. doi: 10.1016/j.lungcan.2017.07.034.
    1. Wakasaki T, Yasumatsu R, Uchi R, et al. Outcome of chemotherapy following nivolumab treatment for recurrent and/or metastatic head and neck squamous cell carcinoma. Auris Nasus Larynx. 2020;47(1):116–122. doi: 10.1016/j.anl.2019.05.001.
    1. Weber JS, Hodi FS, Wolchok JD, et al. Safety profile of nivolumab monotherapy: a pooled analysis of patients with advanced melanoma. J Clin Oncol. 2017;35(7):785–792. doi: 10.1200/JCO.2015.66.1389.

Source: PubMed

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