The positive results from the Phase III RANGE trial offer a new therapeutic option for platinum-refractory advanced or metastatic bladder cancer.
RANGE is the first Phase III trial to show the benefit of targeting angiogenesis in bladder cancer and the first therapy to show superior progression-free survival over chemotherapy in a post-platinum setting. During the Presidential Symposium II, Daniel Petrylak revealed data showing that #Cyramza in combination with docetaxel significantly improved PFS compared with placebo plus docetaxel (4.1 months versus 2.8 months, respectively), corresponding to a 24% reduction in the risk of disease progression. Whether a 1.3 month improvement in PFS is clinically meaningful is debatable! It’s notable that a gatekeeping design was implemented to assess PFS, OS, and ORR in a fixed sequential manner, meaning that an OS analysis will follow now that PFS has been met with statistical significance. Despite having met the primary end point of PFS, Eli Lilly announced earlier this year that “OS results will likely be required for global regulatory submissions” and final OS results are expected in mid-2018. Given that five immune checkpoint inhibitors have already approved in the same setting that Cyramza has been evaluated, delayed time to market in this indication could stymie uptake.
Professor Yohann Loriot, invited discussant of LBA4_PR asked, “will RANGE impact the standard of care for advanced or metastatic bladder cancer?” Multiple approvals of immune checkpoint inhibitors (PD-1/PD-L1 inhibitors) have transformed the treatment algorithm of advanced bladder cancer, at least in the post-platinum setting, making it tough for Cyramza plus docetaxel to penetrate. While data presented show that the addition of Cyramza to docetaxel did not result in any significant additive toxicities, this regimen has a markedly less favorable safety profile than PD-1/PD-L1 monotherapy. When comparing clinical data for Cyramza plus docetaxel with that of Keytruda (the only PD-1/PD-L1 therapy to have Phase III data), Keytruda is superior in terms of 12-year PFS, QoL, and unlike Cyramza plus docetaxel has shown an OS benefit. These factors support a preference for PD-1/PD-L1 over Cyramza plus docetaxel.
However, not all patients will be eligible to receive PD-1/PD-L1 (e.g., autoimmune condition), and of those that do receive PD-1/PD-L1, not all will respond (ORRs are 15-20% in the platinum-refractory setting). It’s significant that the RANGE trial allowed patients to receive one prior immune checkpoint inhibitor (≤24 months from ending a platinum regimen). There are very limited options for platinum-refractory patients, especially for those who progress after immune checkpoint inhibition, as such, Cyramza plus docetaxel might be the third- or late-line treatment of choice after a platinum regimen and immune checkpoint inhibitor therapy.
These data and clinical reasoning support our #Cyramza forecast. Although not displacing the standard of care, #Cyramza plus docetaxel will provide an additional treatment option, impacting the management and sequencing of therapies for advanced or metastatic bladder cancer treatment.
Look out for Decision Resources Group’s upcoming Bladder Cancer Disease Landscape & Forecast, which will include a 10-year market forecast of Cyramza, in combination with docetaxel, in unresectable locally advanced or metastatic urothelial carcinoma. Our new Treatment Sequencing solution helps you identify physicians most frequent treatment sequences in commercially important populations and treatment scenarios. For more insights on oncology drug development, follow @LauraVinuesaDRG
- Petrylak D,et al. RANGE: A randomized, double-blind, placebo-controlled phase 3 study of docetaxel (DOC) with or without ramucirumab (RAM) in platinum-refractory advanced or metastatic urothelial carcinoma. ESMO. 2017. LBA4_PR.
- Lilly press release, May 31, 2017 /PRNewswire/
- Eli Lilly press release, Sept. 10, 2017 /PRNewswire/
- ESMO Daily Reporter, Monday 11 September 2017