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Expert Point of View: Kilian M. Gust, MD


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Formal discussant Kilian M. Gust, MD, of the Medical University of Austria, Vienna, reminded listeners that JAVELIN Bladder 100 was designed at a time when no checkpoint inhibitor was approved for the treatment of metastatic urothelial cancer. In the past 5 years, five immune checkpoint inhibitors have been approved in this setting, including avelumab.

“Second-line pembrolizumab improves overall survival compared with chemotherapy, and both cisplatin and carboplatin improve progression-free survival as first-line therapy. JAVELIN Bladder 100 showed that avelumab as front-line maintenance therapy achieved a clinically meaningful improvement in survival,” Dr. Gust said.

“The subgroup analysis showed that the benefit of avelumab seems to be driven by patients who had a partial response or stable disease on first-line chemotherapy,” he continued.

Kilian M. Gust, MD

Kilian M. Gust, MD

Dr. Gust said it would be useful to compare patients in the best supportive care arm who went on to receive subsequent immunotherapy at disease progression (about 50% of that group) with those treated with avelumab maintenance upfront. He was pleased with the use of a standardized PD-L1 assay in the trial and attributed identifying the high rate of PD-L1 positivity to that strategy.

“Even with immune checkpoint inhibitors, a high number of patients don’t respond, and we need to figure out how to overcome resistance. There is some evidence that PD-L1–positive patients respond, but we need to explore other strategies, such as targeting the tumor microenvironment,” Dr. Gust said. 

DISCLOSURE: Dr. Gust has served as a consultant or advisor to Cepheid, Ferring, Roche, and Merck Sharp & Dohme; has participated in a speakers bureau for Astellas, AstraZeneca, Bristol Myers Squibb, Ipsen, Janssen, Merck Sharp & Dohme, and Roche; and has been reimbursed for travel arrangements or other expenses from Allergen, Astellas, AstraZeneca, Bayer, Bristol Myers Squibb, Janssen, Merck Sharp & Dohme, Novartis, Pfizer, Pierre Fabre, and Roche.

 


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