Use of Immunotherapy for Management of Metastatic Head and Neck Cancers

Educational Objectives

The goal of this program is to improve management of metastatic head and neck cancers (HNCs). After hearing and assimilating this program, the clinician will be better able to:

1. Employ immunotherapy in an evidence-based fashion to treat HNCs.

Summary

History: immunotherapy was first performed in 1891 by Dr. William Coley for a patient with head and neck cancer (HNC); Dr. Coley injected streptococcal bacteria into the tumor to induce infection and tumor shrinkage after noting a similar pattern in patients with sarcoma; the treatment worked and the patient was tumor-free for 8 yr; mixtures of toxins with dead bacteria showed mixed response; radiation and chemotherapy emerged at the time and were deemed safer; checkpoint inhibition — a cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) inhibitor was the first checkpoint inhibitor to receive approval (2011); a programmed cell death protein 1 (PD-1) inhibitor was approved in 2014; most solid tumors now have checkpoint inhibitors and immunotherapy approval

Immunotherapy for platinum-refractory disease: platinum-based chemoradiation or adjuvant platinum and radiation therapy is used for locally advanced disease

Recurrence ≤6 mo: the CheckMate 141 trial and KEYNOTE-012 trial found that median overall survival was 5 mo with standard therapy (single-agent methotrexate, docetaxel, or cetuximab), 7.5 mo with nivolumab, and 8 mo with pembrolizumab, with response rates between 13% and 15%; durable response may be possible with immunotherapy

Recurrence >6 mo after platinum-based treatment, patients without platinum-based treatment, or metastatic disease: the KEYNOTE-048 trial shows that pembrolizumab is superior to cetuximab plus chemotherapy in patients without expression of programmed cell death ligand 1 (PD-L1), and pembrolizumab with chemotherapy is superior to cetuximab plus chemotherapy for patients regardless of PD-L1 expression; thus, immunotherapy plus chemotherapy is administered for patients with PD-L1 negativity; if a patient with PD-L1 positivity, good performance status, and high disease burden needs neoadjuvant treatment, chemotherapy and immunotherapy are provided; if a patient with PD-L1 positivity has low disease burden or is asymptomatic, immunotherapy alone is appropriate; the Tumor Proportion Score (counts positive tumor cells) determines PD-L1 status for lung cancer; the Combined Positive Score (counts positive tumor cells, lymphocytes, and macrophages) determines PD-L1 status for HNCs; results from the KEYNOTE-040 trial reveal a median overall survival similar to that observed in the KEYNOTE-048 trial

Future of immunotherapy: many immunotherapy trials are based on PD-L1 checkpoint inhibitors; combinations with chemotherapy, radiation therapy, and other checkpoint inhibitors (eg, CTLA-4, LAG3) have been tried; the number of trials is decreasing; chemoimmunotherapy is potentially important in nasopharyngeal cancers; CTLA-4 and PD-L1 inhibitors have been tried in a platinum-refractory setting, but no benefits were seen vs standard of care; combining radiation therapy with immunotherapy does not show promising results; addition of immunotherapy to chemoradiation does not offer benefit; tumor mutational burden (TMB) — emerging as a good biomarker; pembrolizumab has been approved for patients with high TMB (present in <5% of HNCs); a positive TMB increases the likelihood for response to immunotherapy

Readings

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 [published correction appears in Lancet. 2020 Jan 25; 395(10220):272] [published correction appears in Lancet. 2020 Feb 22; 395(10224):564] [published correction appears in Lancet. 2021 Jun 12; 397(10291):2252]. Lancet. 2019;394(10212):1915-1928. doi:10.1016/S0140-6736(19)32591-7; Cohen EEW, Soulières 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 [published correction appears in Lancet. 2019 Jan 12; 393(10167):132]. Lancet. 2019;393(10167):156-167. doi:10.1016/S0140-6736(18)31999-8; Ferris RL, Licitra L, Fayette J, et al. Nivolumab in patients with recurrent or metastatic squamous cell carcinoma of the head and neck: efficacy and safety in CheckMate 141 by prior cetuximab use. Clin Cancer Res. 2019;25(17):5221-5230. doi:10.1158/1078-0432.CCR-18-3944; Marcus L, Fashoyin-Aje LA, Donoghue M, et al. FDA approval summary: pembrolizumab for the treatment of tumor mutational burden-high solid tumors. Clin Cancer Res. 2021;27(17):4685-4689. doi:10.1158/1078-0432.CCR-21-0327; McBride S, Sherman E, Tsai CJ, et al. Randomized phase II trial of nivolumab with stereotactic body radiotherapy versus nivolumab alone in metastatic head and neck squamous cell carcinoma. J Clin Oncol. 2021;39(1):30-37. doi:10.1200/JCO.20.00290; Seiwert TY, Burtness B, Mehra R, et al. Safety and clinical activity of pembrolizumab for treatment of recurrent or metastatic squamous cell carcinoma of the head and neck (KEYNOTE-012): an open-label, multicentre, phase 1b trial. Lancet Oncol. 2016;17(7):956-965. doi:10.1016/S1470-2045(16)30066-3; Siu LL, Even C, Mesía 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. doi:10.1001/jamaoncol.2018.4628; Zech HB, Moeckelmann N, Boettcher A, et al. Phase III study of nivolumab alone or combined with ipilimumab as immunotherapy versus standard of care in resectable head and neck squamous cell carcinoma. Future Oncol. 2020;16(36):3035-3043. doi:10.2217/fon-2020-0595.

Disclosures

For this program, members of the faculty and planning committee reported nothing relevant to disclose.

Acknowledgements

Dr. Yilmaz was recorded at the 2022 Multidisciplinary Head and Neck Cancer Update, held on April 18, 2022, in Fort Lauderdale, FL, and presented by the Taussig Cancer Center, Cleveland Clinic, Cleveland, OH. For more information on future CME activities by this presenter, please visit clevelandclinicmeded.com. Audio Digest thanks the speakers and the Taussig Cancer Center, Cleveland Clinic, for their cooperation in the production of this program.

CME/CE INFO

Accreditation:

The Audio- Digest Foundation is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians.

The Audio- Digest Foundation designates this enduring material for a maximum of 0.50 AMA PRA Category 1 Credits™. Physicians should claim only the credit commensurate with the extent of their participation in the activity.

Audio Digest Foundation is accredited as a provider of continuing nursing education by the American Nurses Credentialing Center's (ANCC's) Commission on Accreditation. Audio Digest Foundation designates this activity for 0.50 CE contact hours.

Lecture ID:

ON132103

Expiration:

This CME course qualifies for AMA PRA Category 1 Credits™ for 3 years from the date of publication.

Instructions:

To earn CME/CE credit for this course, you must complete all the following components in the order recommended: (1) Review introductory course content, including Educational Objectives and Faculty/Planner Disclosures; (2) Listen to the audio program and review accompanying learning materials; (3) Complete posttest (only after completing Step 2) and earn a passing score of at least 80%. Taking the course Pretest and completing the Evaluation Survey are strongly recommended (but not mandatory) components of completing this CME/CE course.

Estimated time to complete this CME/CE course:

Approximately 2x the length of the recorded lecture to account for time spent studying accompanying learning materials and completing tests.

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