Disease Analysis: Bladder Cancer

Disease Overview

The most well-established risk factor for bladder cancer is tobacco smoking. Smokers are at approximately a two to four times greater risk of developing bladder cancer than never-smokers, and heavy smokers have a five-fold greater risk of developing the disease. Furthermore, smoking accounts for approximately 47% of bladder cancer cases in the US. Stratified by gender, tobacco use is
estimated to account for 50–65% of bladder cancer in males, and 20–35% of cases in females. Additionally, studies indicate that smoking is strongly associated with a higher risk of developing invasive disease as opposed to low-grade superficial tumors.

Latest key takeaways

• Bladder cancer is the tenth most common cancer worldwide. Datamonitor Healthcare estimates that in 2021, there were 568,700 incident cases of bladder cancer globally, and expects that number to increase to 605,300 incident cases by 2027.
• The majority of bladder cancer diagnoses (77.2%) worldwide are in males, ranging from 70.1% to 78.4% across regions.
• The bladder cancer market will experience rapid growth over the next 10 years across the US, Japan, and five major European markets (France, Germany, Italy, Spain, and the UK). The primary drivers for this growth are label expansions of the established PD-1/PD-L1 drug class and the approval and subsequent uptake of new targeted therapies.
• PD-1/PD-L1 inhibitors remain the dominant class in the bladder cancer market in terms of patient share, and label expansion into earlier disease stages such as non-muscle invasive bladder cancer (NMIBC) and muscle invasive bladder cancer (MIBC) will further grow the overall bladder cancer market.
• Despite the solid performance of PD-1/PD-L1 inhibitors in other settings, poor results from investigations of Keytruda, Imfinzi, and Tecentriq with chemotherapy combinations in front-line platinum-eligible metastatic urothelial carcinoma (mUC) have dampened the likelihood of expansion into this setting of substantial market opportunity.
• Keytruda remains a key therapy across patient segments. Guideline recommendations for use at first line and subsequent lines of therapy, physician familiarity, and an expansion into NMIBC highlight the drug’s broad utility. Though its approval in front-line cisplatin-ineligible mUC was narrowly retained by the FDA, uncertainty persists over the robustness of the data justifying its use in this setting.
• Tecentriq is another PD-1/PD-L1 inhibitor that has encountered regulatory difficulties. The IMvigor010 trial in postoperative MIBC did not meet its primary endpoints, while IMvigor211 failed to show an overall survival benefit over chemotherapy in second-line mUC. These latter findings resulted in Roche withdrawing Tecentriq from the second-line setting following a reappraisal by the FDA. By contrast, Tecentriq’s front-line cisplatin-ineligible label remains unaffected, and positive data from IMvigor130 provide stronger evidence for its use than are available for Keytruda.
• Following the failure of the Phase III DANUBE trial in first-line mUC, AstraZeneca has withdrawn Imfinzi from the bladder cancer indication in line with the conditions imposed by the FDA on its initial approval for previously treated disease. Unlike Tecentriq, this withdrawal removes Imfinzi from the mUC market entirely, and future research is focusing on localized tumors like NMIBC.
• Though Bavencio was initially expected to be the least commercially successful drug in the PD-1/PD-L1 inhibitor class, its use as a maintenance therapy following first-line chemotherapy in mUC satisfies a major unmet need and grants it access to a large and uncontested market. Conversely, the drug’s overall sales will be stymied by a lack of development in other settings.
• With ongoing registration-enabling trials, Opdivo hopes to supplement its currently modest sales within the bladder cancer space with label expansions.
• Antibody-drug conjugates (ADCs) are also expected to contribute to growth of the overall bladder cancer market through continued uptake of Padcev, a label expansion for Padcev in the first-line setting, and the approval of Trodelvy.
• Padcev was the first ADC to be approved for use in bladder cancer. The drug will experience substantial uptake in patients previously treated with platinum-based chemotherapy and a PD-1/PD-L1 inhibitor due to strong clinical data in this population and ongoing development outside of the US. Furthermore, Padcev is being investigated in combination with Keytruda in first-line patients, a larger population that will further the drug’s commercial prospects.
• The newer ADC Trodelvy is expected to have less commercial success than Padcev due to less impressive overall response rate results and a lack of clinical development in previously treated bladder cancer.
• Datamonitor Healthcare expects market growth will be supplemented by the fibroblast growth factor receptor (FGFR) inhibitor drug class, with continued uptake of Balversa – the first drug in this class to be launched – as well as prospective approvals of pipeline FGFR inhibitors such as Truseltiq. However, an FGFR biomarker restriction, as well as the lack of routine FGFR alteration screening, will limit growth within the drug class.
• If approved, the combination of IDO1 inhibitor linrodostat and Opdivo may experience uptake as a peri-adjuvant regimen in MIBC. However, uncertainty surrounding the IDO1 inhibitor class tempers expectations for this combination. Furthermore, linrodostat sales in bladder cancer will be limited due to a lack of development outside of the combination with Opdivo.
• Following Keytruda’s recent launch in the setting, the large and unaddressed market of BCG-resistant NMIBC is set to become highly contested with a suite of novel approvals expected in the coming years including the gene therapy Instiladrin, the recombinant immunocytokine Anktiva, and the anti-CD116 viral therapy CG0070.