StemCell Therapy

Promising results were observed in a small, single-arm, phase 2 studyevaluating the efficacy and safety of the programmed cell death-1 (PD-1)inhibitor, pembrolizumab, plus radiation therapy (RT) in patients with locallyadvanced head and neck cancers who were ineligible to receive cisplatin-basedchemoradiation therapy. These findings were presented during the 2020Multidisciplinary Head and Neck Cancers Symposium in Scottsdale, Arizona.

Cisplatin-based chemoradiation therapyis considered a standard of care for the treatment of locally advanced squamouscell carcinoma of the head and neck (LA-HNSCC), with cisplatin acting as both achemotherapeutic agent and a sensitizer to ionizing radiation. However, it isnot uncommon for patients to have contraindications to the receipt of cisplatintherapy, thereby necessitating selection of another radiosensitizer forconcomitant use with RT.

The choice of pembrolizumab as asubstitute for cisplatin in the setting of LA-HNSCC was based, in part, onprevious studies showing that radiation elicitsand promotes tumor-directed immune-stimulation, which may potentiate antiPD-1therapy, the study authors commented.

None of the 29 adult patients enrolled in this study (ClinicalTrials.gov Identifier: NCT02609503) had undergone prior curative treatment for LA-HNSCC, and an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1 was a study inclusion criterion. Pembrolizumab was administered concurrently with RT every 3 weeks for 3 cycles followed by 3 cycles of pembrolizumab. The primary study endpoint was progression-free survival (PFS), with overall survival (OS) and safety included as secondary study endpoints.

Twenty patients hadcancers of the tongue or tonsil, with a variety of other sites of disease,including supraglottic larynx and hypopharynx, present in the remaining patients.Nonmetastatic stage III or IV disease was present in approximately three-quartersof study patients. Reasons for ineligibility to receive cisplatin includedotopathology (69.0%), nephropathy (20.7%), and neuropathy (6.9%).

One-yearrates of PFS and OS for the overall study population were 76% and 86%,respectively. Furthermore, at a median follow-up of 21 months, the median PFShad not been reached and exceeded the hypothesized median PFS of 16 months,leading study authors to conclude that this approach deserves evaluation in arandomized trial.

Whilerespective 1-year PFS and OS rates were 88% and 94% for patients with p16/humanpapilloma virus (HPV)-positive cancers of the oropharynx, the correspondingrates were 58% and 75% for those with other type of LA-HNSCC.

Although the presence of programmed celldeath-ligand 1 (PD-L1)positive disease was not found to be associated withlikelihood of disease progression, the relative percentages of specific B-cellpopulations, such as a higher percentage of baseline naive B-cells and a lowerpercentage of marginal zone B cells, were associated with an increased risk ofprogressive disease.

Toxicitiesfrequently associated with administration of RT were observed, although grade 3or grade 4 lymphopenia was observed in over half of the study patients.

In their concluding remarks, the study authors stated that concurrent pembrolizumab and radiotherapy has demonstrated promising PFS and OS in LA-HNSCC, regardless of p16 status or anatomic location, with a favorable toxicity profile.

Disclosure: Some of the authors of theabstract disclosed financial relationships with pharmaceutical companies,medical device companies, and/or health-related companies. For a full list ofdisclosures, please refer to the abstract.

Reference

Weiss J, Vincent B, Deal A, et al. Progression-free survival, overall survival and immunophenotyping outcomes for patients with stage III-IV head and neck cancer and cisplatin contraindication treated immunophenotyping outcomes for patients with stage III-IV head and neck cancer and cisplatin contraindication treated with definitive radiotherapy plus pembrolizumab. Presented at: Multidisciplinary Head and Neck Cancers Symposium; February 27-29, 2020; Scottsdale, AZ. Abstract LBA1.

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Promising Clinical Activity for RT Plus ICIs in Locally Advanced Head and Neck Cancers - Cancer Therapy Advisor

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