In This Article:
The FDA has recently approved AstraZeneca’s Imfinzi (durvalumab) for perioperative use in cisplatin-eligible muscle-invasive bladder cancer (MIBC), based on the Phase III NIAGARA trial. With its practice-changing regimen, Imfinzi is the first immunotherapy approved for neoadjuvant treatment, as it is administered in combination with chemotherapy in this setting and postoperatively as monotherapy.
At 24 months, the NIAGARA study met its primary endpoint of event-free survival, besting the platinum-based chemotherapy standard of care (SOC) with 67.8% versus 59.8% (hazard ratio [HR], 0.68). The regimen also reduced the risk of death by 25%, with overall survival at two years reaching 82% versus 75% in the control arm (HR, 0.75). The recent GlobalData patient-based forecast estimates Imfinzi’s sales in bladder cancer to reach $640 million by 2033 across the eight major markets (8MM: China, France, Germany, Italy, Japan, Spain, the UK and the US).
While the approval is considered practice-changing, some key opinion leaders expressed reservations, citing concerns about potential overtreatment in both the neoadjuvant and adjuvant settings. A similar concern delayed FDA approval in the AEGEAN trial for perioperative stage II–IIIb non-small cell lung cancer. However, data from CheckMate 274, in which Opdivo improved disease-free survival postoperatively even in patients with a complete response (CR) to neoadjuvant therapy, supports the potential value of adjuvant immunotherapy.
Multiple other candidates are competing for space in the perioperative bladder cancer landscape. For cisplatin-ineligible patients, excitement is building around the antibody-drug conjugate Padcev in combination with Keytruda (KEYNOTE-905/EV-303), already SOC in first-line metastatic bladder cancer. This regimen could allow patients to avoid chemotherapy in the neoadjuvant setting, potentially preserving surgical fitness. For cisplatin-eligible patients, the same combination (KEYNOTE-B15/EV-304) must demonstrate clear advantages in CR or survival over the NIAGARA regimen to justify a shift in SOC and higher associated costs.
In the adjuvant setting, Opdivo maintains a first-mover advantage with approval for both cisplatin-eligible and ineligible patients, unlike Keytruda, which is currently limited to the cisplatin-ineligible population. Meanwhile, biomarker-driven strategies are emerging: the ongoing IMvigor011 study is evaluating Tecentriq (atezolizumab) in patients who are circulating tumour DNA-positive after neoadjuvant chemotherapy. If successful, the trial could establish a new standard for risk-adapted, biomarker-guided adjuvant therapy.