ESMO26: VOLGA stirs up perioperative bladder cancer therapy
VOLGA investigator Thomas Powles presenting the results at ESMO.
A perioperative regimen for muscle-invasive bladder cancer (MIBC) based on AstraZeneca's Imfinzi and Astellas/Pfizer's Padcev has improved survival in the VOLGA study, but the jury is out on whether it will displace a rival, established alternative.
VOLGA was conducted in patients with MIBC ineligible or unwilling to take platinum-based chemotherapy, who received PD-L1 inhibitor Imfinzi (durvalumab) before and after surgery to remove the tumour, and Nectin-4-targeting Padcev (enfortumab vedotin) before surgery only.
The main result was a 42% reduction in the risk of death compared to standard therapy based on surgery to remove the bladder altogether, putting a number on a top-line result first disclosed in May. Meanwhile, event-free survival (EFS) was improved by 49%, at 23 months for the drug group and 12.1 months for the control. Adding AZ's CTLA4 inhibitor Imjudo (tremelimumab) to the regimen delivered no added benefit.
The results were published in the New England Journal of Medicine alongside the presentation at ESMO by lead investigator Thomas Powles of Barts Health NHS Trust.
"Patients with muscle-invasive bladder cancer require life-changing bladder removal surgery. Despite this, the cancer returns in about half of patients," he said. "These practice-changing results support this approach as a patient-centric, potential new standard of care in this setting."
The big debate at ESMO was how the result fits in with evolving views on neoadjuvant and adjuvant drug therapy in MIBC, in light of the impressive results seen with a regimen based on MSD's Keytruda (pembrolizumab) and Padcev, both given before and after surgery to cisplatin-ineligible patients, in the KEYNOTE-905 and KEYNOTE-B15 trials.
It also raises a question for Padcev, which would see its use truncated in the adjuvant setting if the VOLGA data proves compelling for oncologists. One consideration is that the regimen had relatively low rates of peripheral neuropathy, a recognised Padcev side effect, which could make it more attractive for patients.
On the other hand, it's unclear whether some patients would derive further benefit from adjuvant use of Padcev, according to ESMO commentator Michiel van der Heijden of the Netherlands Cancer Institute, who said that this should be the subject of future investigations.
"Data on ADCs plus immune checkpoint inhibitors in bladder cancer are now robust and consistent, whereas immune checkpoint inhibitors and chemotherapy in bladder cancer have shown less consistency," added van der Heijden.
Bladder cancer has been billed by AZ as a "meaningful new opportunity" for Imfinzi, which brought in more than $6 billion in sales for AZ last year is already approved as a peri-operative regimen for MIBC in combination with platinum chemo, based on the NIAGARA trial, along with other indications in gastric, lung, liver, endometrial, and biliary tract cancers.
