Pembrolizumab plus radiation effective, safe in locally advanced head and neck squamous cell carcinoma
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Pembrolizumab in combination with radiotherapy conferred promising survival outcomes with acceptable toxicity among patients with locally advanced head and neck squamous cell carcinoma, according to results of a single-arm phase 2 study presented at Multidisciplinary Head and Neck Cancers Symposium.
The effectiveness appeared consistent regardless of p16 status or anatomic location.
Researchers noted that changes observed in B-cell markers deserve further study, both as potential biomarkers of treatment response and as therapeutic targets.
Cisplatin plus radiotherapy is the current standard of care for patients with locally advanced HNSCC. However, adverse events associated with cisplatin limit use of the platinum-based chemotherapy.
“This is a common dilemma in the exam room because cisplatin, [although] effective, tends to be particularly toxic for patients and can lead to permanent side effects for some,” Jared Weiss, MD, associate professor of medicine at The University of North Carolina Lineberger Comprehensive Cancer Center, said in a press release. “I will have patients I want to treat with platinum chemotherapy, but I also want to align treatment with their values. Is the patient willing to accept a risk for deafness or exacerbated ringing in their ears? These are not acceptable consequences for most people.”
Radiation therapy elicits and promotes tumor-directed immune stimulation; thus, it may enhance the effects of anti-PD-1 therapy, researchers wrote.
Weiss and colleagues investigated the efficacy of the PD-1 inhibitor pembrolizumab (Keytruda, Merck) and radiotherapy among 29 patients with stage III or stage IV locally advanced HNSCC disease who were ineligible for cisplatin chemotherapy. Reasons for cisplatin ineligibility included otopathology (69%), nephropathy (20.7%) and neuropathy (6.9%).
Primary cancer sites included the base of the tongue (n = 10), tonsil (n = 10), supraglottic larynx (n = 3), hypopharynx (n = 2), oral tongue (n = 1) and uvula (n = 1).
Researchers assigned patients to radiotherapy concurrently with three cycles of pembrolizumab, dosed at 200 mg, over 6 weeks followed by three adjuvant cycles of pembrolizumab.
PFS of at least 16 months served as the study’s primary endpoint.
Results showed a 1-year PFS rate of 76% (95% CI, 56-88) and a 1-year OS rate of 86% (95% CI, 67-95).
The study exceeded its primary endpoint, with median PFS not reached after median follow-up of 21 months.
Among patients with p16-positive oropharynx cancer (n = 17), researchers observed a 1-year PFS rate of 88% (95% CI, 61-97) and 1-year OS rate of 94% (95% CI, 65-99). The other patients (n = 12) had lower rates of 1-year PFS (58%; 95% CI, 27-80) and 1-year OS (75%; 95% CI, 41-91).
Median OS had not been reached.
More than half of patients (58.6%) experienced grade 3 or grade 4 lymphopenia, but most toxicities were mild and typical of radiotherapy. Flow cytometry showed a relative decline in CD4 and B cells, although this did not apply to CD8 cells. Frequencies of transitional B cells and tissue-like memory B cells increased following treatment, whereas resting memory B cells decreased. Patients who experienced progression had higher proportions of baseline naïve B cells and fewer marginal zone B cells.
PD-L1 did not distinguish patients with or without progression, and cytokine profiles did not change significantly through therapy, researchers wrote.
"If you look back to the historic studies, radiation alone often cures patients with this disease,” Weiss said in the press release. “Some of the first patients treated with pembrolizumab for recurrent/metastatic cancer are still alive many years out, with no evidence of disease. And so, our concept was that, in addition to whatever synergy the immunotherapy might provide with radiation, we also conceived of it in a more straightforward way as a ‘second shot on goal’ toward cure.” – by John DeRosier
Reference:
Weiss J, et al. Abstract LBA 1. Presented at: Multidisciplinary Head and Neck Cancers Symposium; Feb. 27-29, 2020; Scottsdale, Arizona.
Disclosures: Weiss reports research funding from and/or consultant/advisory roles with AbbVie, Amgen, AstraZeneca, Azitra, Blueprint Medicines, Eli Lilly, EMD Serono, Inivata and Jounce Therapeutics; honoraria from G1 Therapeutics; and stock ownership in Nektar Therapeutics. Please see the abstract for all other researchers’ relevant financial disclosures.