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Led EV-302, NIAGARA and IMvigor011, the trials that transformed bladder cancer from chemotherapy-only to ADC, immunotherapy and ctDNA-guided care.
Thomas Powles was principal investigator of EV-302, which showed enfortumab vedotin plus pembrolizumab nearly doubles survival versus chemotherapy in first-line advanced urothelial cancer, of NIAGARA (perioperative durvalumab), of JAVELIN Bladder 100 (avelumab maintenance) and of IMvigor011, the first trial to show ctDNA can select who benefits from adjuvant immunotherapy. He also led KEYNOTE-426 and CLEAR analyses in kidney cancer. He is among the most cited investigators in GU oncology.
After bladder removal, a blood test can now tell who needs immunotherapy and who can safely be spared it. This is the model for MRD-guided adjuvant therapy across cancers: treat the blood-positive, watch the blood-negative.
Almost every patient newly diagnosed with advanced bladder or urothelial cancer should now be offered enfortumab vedotin plus pembrolizumab rather than chemotherapy, with median survival extended from about 16 months to over two and a half years. Neuropathy and skin toxicity need monitoring and dose adjustment, and patients with severe diabetes or pre-existing neuropathy need care. Platinum chemotherapy remains an option for those who cannot receive the combination.
Patients fit enough for cisplatin whose bladder cancer has invaded the muscle wall should now be offered durvalumab with their pre-operative chemotherapy and for about a year after surgery, which improves the chance of cure without compromising the operation. The trial cannot say whether the adjuvant phase is necessary, or how to treat cisplatin-ineligible patients, for whom other trials are ongoing.
Shares EV-302 / KEYNOTE-A39, Nectin-4, EV-302: enfortumab vedotin plus pembrolizumab replaces chemotherapy as first treatment for advanced bladder cancer, Enfortumab vedotin and the tags urothelial, adc.
Shares Atezolizumab, PD-L1, PD-1, Bladder & urothelial cancer and the tag urothelial.
Shares KEYNOTE-426, Renal cell carcinoma, PD-1, Pembrolizumab and the tag trialist.
Shares KEYNOTE-426, EV-302 / KEYNOTE-A39, Enfortumab vedotin, Renal cell carcinoma.
Shares IMvigor011: using a blood test for leftover cancer to decide who gets immunotherapy after bladder surgery, IMvigor011, Signatera, ctDNA tests roadmap: from a curiosity in plasma to blood tests that decide treatment.
Shares Antibody-drug conjugate (ADC) and the tags adc, trialist.
Shares Barts Cancer Institute / Barts Health NHS Trust, Atezolizumab, PD-L1, PD-1 and the tag trialist.
Shares PD-1, Bladder & urothelial cancer, Pembrolizumab, Immune checkpoint inhibitors and the tag urothelial.