- Email: [email protected]
Pembrolizumab in advanced head and neck cancer
News
In a single-arm phase 2 study (KEYNOTE-055), patients with recurrent or metastatic squamous cell head and neck cancer received the PD-1 inhibitor pembrolizumab within 6 months of previous platinum or cetuximab treatment. 28 (16% [95% CI 11–23]) of 171 patients achieved an overall response, with a median duration of response of 8 months (range 2+ to 12+). After a median follow-up of 7 months (range 0–17), 21 (75%) of 28 patients had an ongoing response; median progression-free survival was 2·1 months (95% CI 2·1–2·1) and median overall survival was 8 months (95% CI 6–11). 109 (64%) of 171 patients had treatment-related adverse events; 26 (15%) patients had a grade 3 or worse adverse event, the most frequent being an increase in aspartate amino transferase (four patients [2%]). Treatment was discontinued in seven
(4%) patients and one patient died of treatment-related pneumonitis. “Our study, which demonstrates an improvement over the standardof-care, was designed and completed before the approval in the USA of pembrolizumab for progression within 6 months of therapy in platinum-resistant disease,” said first author Joshua Bauml (University of Pennsylvania, Philadelphia, PA, USA). “We are seeing a convergence of data with regard to response to anti-PD1 therapy in heavily pretreated head and neck cancer,” said Maura Gillison (MD Anderson Cancer Center, Houston, TX, USA). “As these agents become incorporated into earlier treatment regimens, we may see a greater signal for activity in specific subsets, such as HPVpositive, inflamed tumours, and those with high mutation rates,” Gillison said. 140 (82%) of 171 patients were PD-L1 positive using a cutoff of 1% or
higher PD-L1 positive cells in both the tumour and stroma; 25 (18% [95% CI 12–25]) of these patients achieved an overall response whereas three (12% [95% CI 2–30]) of 26 patients who were PD-L1-negative achieved a response. “Patients with higher levels of PD-L1 in tumours and in the microenvironment had slightly better response rates, which is also seen in studies in patients with non-smallcell lung cancer with PD-1 inhibitors,” said Barbara Burtness (Yale University School of Medicine, New Haven, CT, USA). “These studies measured not only expression [of PD-L1] on cancer cells, but also in the surrounding inflammatory cells,” “Going forward, measuring both could be important in identifying groups who might have higher response rates with these drugs,” she added.
Steve Gschmeissner/Science Photo Library
Pembrolizumab in advanced head and neck cancer
Lancet Oncol 2017 Published Online March 30, 2017 http://dx.doi.org/10.1016/ S1470-2045(17)30245-0 For the KEYNOTE-055 study see J Clin Oncol 2017; publishedonline March 27. DOI:10.1200/JCO.216.70.1524
Vicki Brower
www.thelancet.com/oncology Published online March 30, 2017 http://dx.doi.org/10.1016/S1470-2045(17)30245-0
1
In a single-arm phase 2 study (KEYNOTE-055), patients with recurrent or metastatic squamous cell head and neck cancer received the PD-1 inhibitor pembrolizumab within 6 months of previous platinum or cetuximab treatment. 28 (16% [95% CI 11–23]) of 171 patients achieved an overall response, with a median duration of response of 8 months (range 2+ to 12+). After a median follow-up of 7 months (range 0–17), 21 (75%) of 28 patients had an ongoing response; median progression-free survival was 2·1 months (95% CI 2·1–2·1) and median overall survival was 8 months (95% CI 6–11). 109 (64%) of 171 patients had treatment-related adverse events; 26 (15%) patients had a grade 3 or worse adverse event, the most frequent being an increase in aspartate amino transferase (four patients [2%]). Treatment was discontinued in seven
(4%) patients and one patient died of treatment-related pneumonitis. “Our study, which demonstrates an improvement over the standardof-care, was designed and completed before the approval in the USA of pembrolizumab for progression within 6 months of therapy in platinum-resistant disease,” said first author Joshua Bauml (University of Pennsylvania, Philadelphia, PA, USA). “We are seeing a convergence of data with regard to response to anti-PD1 therapy in heavily pretreated head and neck cancer,” said Maura Gillison (MD Anderson Cancer Center, Houston, TX, USA). “As these agents become incorporated into earlier treatment regimens, we may see a greater signal for activity in specific subsets, such as HPVpositive, inflamed tumours, and those with high mutation rates,” Gillison said. 140 (82%) of 171 patients were PD-L1 positive using a cutoff of 1% or
higher PD-L1 positive cells in both the tumour and stroma; 25 (18% [95% CI 12–25]) of these patients achieved an overall response whereas three (12% [95% CI 2–30]) of 26 patients who were PD-L1-negative achieved a response. “Patients with higher levels of PD-L1 in tumours and in the microenvironment had slightly better response rates, which is also seen in studies in patients with non-smallcell lung cancer with PD-1 inhibitors,” said Barbara Burtness (Yale University School of Medicine, New Haven, CT, USA). “These studies measured not only expression [of PD-L1] on cancer cells, but also in the surrounding inflammatory cells,” “Going forward, measuring both could be important in identifying groups who might have higher response rates with these drugs,” she added.
Steve Gschmeissner/Science Photo Library
Pembrolizumab in advanced head and neck cancer
Lancet Oncol 2017 Published Online March 30, 2017 http://dx.doi.org/10.1016/ S1470-2045(17)30245-0 For the KEYNOTE-055 study see J Clin Oncol 2017; publishedonline March 27. DOI:10.1200/JCO.216.70.1524
Vicki Brower
www.thelancet.com/oncology Published online March 30, 2017 http://dx.doi.org/10.1016/S1470-2045(17)30245-0
1