Padcev Approval Gives Another Option to Treat Bladder Cancer

The FDA recently expanded the indication of a drug for certain types of urothelial cancer, the most common form of bladder cancer. Payers and oncologists appear to be divided, however, on the drug’s place in a treatment regimen. But in a therapeutic class with limited therapeutic options, the approvals are a welcome addition, particularly in the second-line setting.

On July 9, the FDA gave an additional approval to Astellas Pharma US, Inc. and Seagen Inc.’s Padcev (enfortumab vedotin-ejfv) for the treatment of adults with locally advanced or metastatic urothelial cancer who are ineligible for cisplatin-containing chemotherapy and have received at least one line of therapy. The agency also converted the Nectin-4-directed antibody and microtubule inhibitor conjugate’s accelerated approval, granted Dec. 18, 2019, to regular approval for the treatment of adults with locally advanced or metastatic urothelial cancer who have received a programmed death receptor-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibitor and a platinum-containing chemotherapy before or after surgery or in a locally advanced or metastatic urothelial cancer setting.

Payers, Providers Have Different Views

For the Managed Care Oncology Index: Q1 2021, between Feb. 26, 2021, and April 9, 2021, Zitter Insights polled 40 commercial payers with 132.2 million covered lives and found respondents cited a handful of immunotherapies as their top bladder cancer drugs. Respondents covering 36% of lives said Tecentriq (atezolizumab) from Genentech USA Inc., a member of the Roche Group, is their ideal first-line bladder cancer therapy, followed closely by Keytruda (pembrolizumab) from Merck & Co., Inc. The latter agent recently received an updated approval in this indication. Moreover, respondents with 31% of covered lives said that AstraZeneca’s Imfinzi (durvalumab) was their top second-line therapy, followed by those with 27% of lives who cited Bristol-Myers Squibb Co.’s Opdivo (nivolumab), which also got another approval in urothelial carcinoma in August.

Zitter Insights and AIS Health are both MMIT companies.

During the same time frame, Zitter Insights polled 100 oncologists about bladder cancer. While 43% of them selected Keytruda as their ideal first-line therapy, Padcev was tapped as the top second-line therapy, cited by 28% of respondents, some of whom pointed to its “good activity and response rate.” Among oncologists’ prescribing of bladder cancer agents over the 12 months prior to the survey, Keytruda was the top drug, prescribed by 82% of respondents. Almost half — 48% — had prescribed Padcev.

“Padcev’s approval brings the ability to administer a second-line approved regimen to the metastatic/advanced bladder cancer patient who has either failed cisplatin/IO [i.e., immunotherapy] or is cisplatin-ineligible, which is estimated to be approximately 50% of the patients at this stage,” observes Winston Wong, Pharm.D., president of the W-Squared Group. “Previous to this approval, regimens were either not approved or off-label.”

Adds Mesfin Tegenu, CEO of RxParadigm, “this approval provides the class additional options for providers and patients to consider after previously receiving one more other therapies. It is the first FDA-approved therapy for patients with locally advanced or metastatic cancer who cannot receive cisplatin.”

Asked if bladder cancer is a class of concern for payers, Tegenu says yes because it’s “one of the most costly cancer classes to treat. One of the key factors that may impact statistics is the lack of compliance to treatment guidelines.”

“All oncology is a concern to payers, mainly due to the cost,” says Wong. “The question is really how much of a concern. In the case of bladder cancer, cisplatin-based chemotherapy is relatively inexpensive compared to the IOs or targeted therapies. The IOs are now being used in metastatic/advanced disease after cisplatin failure, which does bump the cost curve. Padcev will have an approximate cost of $35,000 per month and a total annual cost of around $450,000 depending upon how long the patient responds. Following cisplatin/IO failure,…the average survival is around 13 months. In patients who are cisplatin-ineligible, the time to progression is around 12 months. Thus, patients will most likely be on Padcev for 12 months on average. If the patient is on Padcev for 12 months, it does become an even higher concern for payers; however, with so few approved treatment options in metastatic/advanced bladder cancer, there is not much a payer can do but to ensure that the drug is being used to the labeled indication, especially with the black box warning.”

“Due to the various stages, high recurrence rate, complications and monitoring required, the average cost for a member with bladder cancer will vary,” Tegenu tells AIS Health. “The lifetime cost for a patient with bladder cancer can be upwards of a hundred thousand dollars.”

Wong cites an August 2020 article in the European Urology Oncology journal that examined bladder cancer care costs in Medicare. Researchers found that “the incremental costs (above those associated with controls) were highest during the first year after diagnosis and were dependent on the extent of the cancer,” he says. “Metastatic or distant cancer had an average cost of $47,533, regional cancer was $42,403, and localized cancer was $14,304. Bladder cancer survival was highly stage-dependent. Since bladder cancer has approximately a 70% survival rate, survivor cost for follow-up initially spikes for one to two years, then drops. Long-term survivors in the full sample accrued cumulative Medicare costs of $172,426 over 16 years — 46% higher than for controls.”

Management of Class Can Be Challenging

Payers, Tegenu says, “need to consider the risk, stage and possible reoccurrence and complications in order to manage this class of drugs, which may pose as a challenge given patient-specific variables.”

Generally, says Wong, “any management of bladder cancer will be limited to approved indications for the medications being utilized or consistency with the accepted treatment guidelines.…Bladder cancer is usually treated surgically, the extent of which depends on the level of muscle invasion. Neoadjuvant and adjuvant cisplatin-based chemotherapy are indicated in patients undergoing cystectomy. For metastatic or advanced disease, a cisplatin-based chemotherapy regimen is still the initial approach. Checkpoint inhibitors are used in patients who have progressed during or after a cisplatin-based chemotherapy or in patients where cisplatin is not indicated.”

In bladder cancer, “while some payers may indicate covered therapies, treatment options are dependent on age, stage and expected life span among other factors,” states Tegenu. “With the high cost of treatment and challenges of access to care, there are programs that have implemented value-based payment models to address care, chemotherapy treatment and hospitalization related to treatment for cancer patients.”

“Payers will have preferred medications at every opportunity, when there are multiple medications that provide the similar clinical benefits and cost savings opportunities,” Wong tells AIS Health. “Only the more aggressive plans that have clinical pathway programs in place will have preferred therapies. However, in this case, due to so few treatment options being available for the metastatic/advanced bladder cancer patient, I am not sure a clinical pathway would be applicable, beyond that of reducing the amount of variable of treatment administered with little clinical justification.”

According to Tegenu, among people with bladder cancer, “prevalent comorbidities are diabetes and renal disease. Comorbid conditions have been shown to lead to further complications for a subset of bladder cancer populations, such as those who underwent cystectomy.”

Even with newer FDA approvals in the class, more therapies are needed. Tegenu points to a promising PD-1 inhibitor in the pipeline, Pfizer Inc.’s sasanlimab (PF-06801591), which is in a Phase III clinical trial in combination with Bacillus Calmette-Guerin for people with high-risk non-muscle invasive bladder cancer. The agent “is administered subcutaneously, which is a unique delivery system and selling point compared to current therapy,” he maintains.

“There is a need for more approved treatment options for patients with metastatic/advanced bladder cancer,” asserts Wong. “First-line is a cisplatin-based regimen, with or without a PD-1 or PD-L1 inhibitor. Padcev will now become the second-line treatment. If a patient continues to progress on Padcev, there are no approved treatment options, and there is no standard of care. At least for now, the standard of care is slightly expanded.”

Contact Tegenu at Mesfin.Tegenu@rxparadigm.com and Wong at w2sqgroup@gmail.com. For more information on the Zitter data, contact Jill Brown Kettler at jbrown@aishealth.com.

This story was reprinted from AIS Health’s monthly publication RADAR on Specialty Pharmacy.