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Enfortumab+pembrolizumab combination as the 1st line treatment of choice for advanced urothelial cancer – summary by Piotr J. Wysocki
Mar 15, 2024, 15:26

Enfortumab+pembrolizumab combination as the 1st line treatment of choice for advanced urothelial cancer – summary by Piotr J. Wysocki

Piotr J. Wysocki, Professor of Medicine, Head of Department of Oncology at Jagiellonian University Hospital, recently shared on LinkedIn:

“A pre-proof of ESMO interim updated guidelines in urothelial cancer has been just (March 13) published online in Annals of Oncology. Powles T et al. have defined the current standard of care in 1st line treatment as the combination of enfortumab vedotin and pembrolizumab based on the results of the EV302 study. All eligible patients should be offered this combination in 1st line setting with optional 2nd line treatment consisting of platinum-based chemotherapy or FGFR inhibitor (in patients with somatic FGFR2,3 rearrangements).

Other treatment options in 1st line settings can be considered only if enfortumab vedotin+pembrolizumab combination is unavailable or contraindicated. The options include a combination of nivolumab+gemcitabine+cisplatin only in cisplatin-eligible patients and gemcitabine+cisplatin/carboplatin with avelumab maintenance in the case of eligibility for platinum-based chemotherapy.

The guidelines reflect the very high activity of enfortumab vedotin+pembrolizumab combination observed in EV302 study when the investigational long-term therapy was compared to gemcitabine+platinum combination with significantly improved OS, PFS and ORR. However, it is worth noting that patients in the comparator arm were not treated according to current guidelines, with only approx. 30% of patients treated with avelumab maintenance after 18 weeks of initial chemotherapy (63% of eligible patients have not received maintenance therapy).

Additionally, patients in the investigational arm were treated continuously until progression, while patients in the control arm received chemotherapy for a maximum of up to 6 cycles, which was stopped irrespectively of response. One also has to remember that the chemotherapy-related adverse events were short-lasting while patients receiving the combination therapy faced long-term (until progression) AEs such as peripheral sensory neuropathy, ocular disorders, pruritus, or rash.

There still may be patients who might benefit from the standard chemotherapy approach with maintenance avelumab even in the availability/reimbursement of enfortumab+pembrolizumab combination – asymptomatic patients with low disease burden, good performance status and eligible for cisplatin-based chemotherapy.”

Source: Piotr J. Wysocki/LinkedIn