New Treatments For Bladder Cancer in 2020

In-Depth Insights |  Written by Emma Shtivelman, PhD

Emma Shtivelman, PhD

In 2019 and early 2020, the U.S. Food and Drug Administration (FDA) approved a number of new drugs for bladder cancer of all stages, and more treatments are on the horizon. Here’s a snapshot of what’s happening right now in bladder cancer treatment:

Non-muscle invasive bladder cancer (NMIBC)

In patients with NMIBC, tumors are confined to the inner cell layer of the bladder and have not invaded the thick muscle tissue of the bladder. NMIBC is usually treated by surgical excision in a procedure known as trans urethral resection of bladder tumor (TURBT), followed by repeated drug injections into the bladder (intravesical injection)—most commonly with a drug called Bacillus Calmette-Guerin (BCG).

BCG is a bacterial vaccine that is primarily used to immunize against tuberculosis, but may also trigger a broader immune response against cancer cells. BCG certainly improves outcomes for patients whose tumors have been resected; nevertheless, over a half of these patients will experience recurrence within one year, and some do not respond to BCG at all. Intravesical chemotherapy drugs (gemcitabine or mitomycin) are used for higher-grade NMIBC.

Newly emerging options for NMIBC include:

  • A new version of BCG, still in development, called VPM1002. Clinical testing suggests it is effective in more than half of patients who have no response to standard BCG.
  • A gel form of mitomycin, UGN101. The FDA recently granted a priority review designation to this drug for low-grade NMIBC. In a clinical study, 59% of patients with recurrent cancer achieved complete response, and 84% of them have not experienced a recurrence within a year.
  • A new, viral-based version of interferon (immune cytokine), called nadofaragen firadenovec (Instilidrin). While interferon is not used very much these days, nadofaragen firadenovec produced durable responses in 53% of patients with high-grade NMIBC that did not respond to BCG treatment.

Of course, the biggest news for NMIBC is the recent FDA approval of the immune checkpoint drug pembrolizumab (Keytruda) for systemic (intravenous) treatment of high grade NMIBC that is not responsive to BCG. In clinical testing, 41% of patients experienced complete responses with median duration of 16 months.

Muscle-invasive bladder cancer (MIBC), not metastatic 

A far more threatening form of bladder cancer, MIBC is often treated by partial or complete removal of the bladder, usually after pre-surgery (neoadjuvant) chemotherapy, sometimes with concurrent radiation. After the tumor (or bladder) excision (adjuvant), more chemotherapy may be given.

A very recent report documented complete pathologic responses (no tumor detected) after neoadjuvant chemotherapy in 49% of NIBC patients who, in addition to chemotherapy, received the immune checkpoint drug nivolumab (Opdivo). Another 17% of patients still had tumors, but they no longer invaded the muscle.

Another immune checkpoint drug, durvalumab (an anti-PD-L1 drug, brand name Imfinzi), combined with olaparib (a PARP1 inhibitor, brand name Lynparza) in a small trial produced complete pathologic responses in 50% of patients prior to tumor resection.

Atezolizumab (Tecentriq), also an anti-PD-L1 drug, failed to prolong disease-free survival when used as adjuvant treatment in MIBC.

Advanced and metastatic bladder cancer

A notable new FDA approval in December 2019 was enfortumab vedotin (Padcev), approved for advanced bladder cancer patients who have not responded to chemotherapy or immune checkpoint drugs. In clinical testing, this antibody-drug conjugate produced responses in 44% of patients who failed to benefit from chemotherapy or immune checkpoint drugs.

It is worth noting that while the drugs atezolizumab and pembrolizumab were previously FDA-approved as first-line treatments for metastatic bladder cancer, both were later shown to have some benefit only in patients with PD-L1 positive cancers, and the label was modified accordingly, limiting availability of these two immune drugs to a smaller number of patients.

Also in December 2019, the FDA granted a breakthrough therapy designation to the combination of enfortumab with pembrolizumab, based on a preliminary response rate of 63% in patients ineligible for chemotherapy, and a disease control rate of 90%. These are truly impressive results,.

The combination of atezolizumab with chemotherapy as a first-line treatment has also produced promising results, but a combination of two immune drugs—durvalumab and tremelimumab—has failed in comparison to chemotherapy alone.

Nearly 30% of bladder cancers have alterations in the genes FGFR3 or FGFR2, and earlier in 2019, the FDA granted approval to erdafitinib (Balversa) for this subgroup. In clinical testing, erdafitinib showed a 32% overall response rate, which included just over 2% complete responses.

Clearly, the repertoire of drugs for bladder cancer—both approved and in clinical trials—has greatly expanded over barely one year, with new immunotherapies, new targeted drugs, and combinations thereof.

If you’re wondering whether any of this information applies to your own cancer case or a loved one’s, I invite you to get support from Cancer Commons.

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