The IMvigor210 trial (ClinicalTrials.gov Identifiers: NCT02951767, NCT02108652) spanned 47 academic medical centers and community oncology practices in 7 countries. One hundred and nineteen cisplatin-ineligible patients received 1200 mg of atezolizumab intravenously every 21 days.6
“At 17.2 months’ median follow-up, the objective response rate was 23%…and 19 of 27 responses were ongoing,” the study reported.
A separate study, the KEYNOTE-052 (ClinicalTrials.gov Identifier: NCT02335424), made a similar analysis of pembrolizumab, with similar results.7 The FDA granted priority review to a supplemental Biologics License Application for first-line use of the immunotherapy in January.8 The agency is expected to take action by June 14.
“That raises the possibility that there is a subset of patients who may not need chemotherapy at all,” Dr Balar said.
It also offers a line of treatment for the 30% to 50% of patients with advanced bladder cancer considered cisplatin-ineligible because of their age, renal function, or other medical conditions.
In late February, the FDA also granted a priority review for another immunotherapy treatment, avelumab, as a second-line treatment for patients whose cancer progressed after platinum-based chemotherapy.9 The review came as a result of a phase 1b study of 44 patients that found objective response rates of 18.2%.10
The lead author of the study, Andrea B. Apolo, MD, head of the bladder cancer section of the Genitourinary Malignancies Branch at the National Cancer Institute in Bethesda, Maryland, said it added to the evidence that PD-1/PD-L1 inhibitors offer “a new treatment paradigm in bladder cancer.”
“We’re in a new era where we will probably be using these checkpoint inhibitors as backbone in combination with other therapies to see if we can enhance the activity that we’re seeing.”
In other words, Dr Apolo said, research will focus on increasing the response rates through a variety of avenues.
That includes novel combinations that are yielding promising results. She, for example, has combined cabozantinib, a targeted therapy tyrosine kinase inhibitor, with a checkpoint inhibitor.
“It seems to affect the microenvironment so it stimulates the immune cells,” she said. “We’re seeing some very nice activity, even higher responses than we would with a checkpoint inhibitor alone.”
RELATED: Bladder-sparing Therapy Outcomes Similar to Cystectomy in Bladder Cancer
Some of those therapeutic approaches may help patients with localized cancer avoid aggressive chemotherapy or surgical removal of the bladder, Dr Balar said. And recent developments point to even more therapeutic advances, sooner rather than later.
“The pace of science and discovery that is happening in bladder cancer today is unmatched in its prior history,” Dr Balar said. “If there were ever a time to say that this is a fast-moving field it would be now. And that was really never the case before.”
As if to prove his point, the FDA granted accelerated approval as a second-line treatment to yet another immunotherapy, durvalumab, on May 1.
- Cancer stat facts: bladder cancer. National Cancer Institute website. https://seer.cancer.gov/statfacts/html/urinb.html. Accessed April 2017.
- Askeland EJ, Newton MR, O’Donnell MA, Luo Y. Bladder cancer immunotherapy: BCG and beyond. Adv Urol. 2012;2012:181987. doi: 10.1155/2012/181987
- FDA approves new, targeted treatment for bladder cancer [news release]. Silver Spring, MD: US Food and Drug Administration; May 18, 2016. https://www.fda.gov/NewsEvents/Newsroom/ PressAnnouncements/ucm501762.htm. Accessed April 2017.
- Nivolumab for treatment of urothelial carcinoma [news release]. Silver Spring, MD: US Food and Drug Administration; February 2, 2017. https://www.fda.gov/drugs/informationondrugs /approveddrugs/ucm539646.htm. Accessed April 2017.
- FDA grants Genentech’s Tecentriq (atezolizumab) accelerated approval as initial treatment for certain people with advanced bladder cancer [news release]. South San Francisco, CA: Genentech; April 17, 2017. https://www.gene.com/media/press-releases/14660/2017-04-17/fda-grants-genentechs-tecentriq-atezoliz. Accessed April 2017.
- Balar AV, Galsky MD, Rosenberg JE, et al. Atezolizumab as first-line treatment in cisplatin-ineligible patients with locally advanced and metastatic urothelial carcinoma: a single-arm, multicentre, phase 2 trial. Lancet. 2017;389(10064):67-76. doi: 10.1016/S0140-6736(16)32455-2
- Balar A, Bellmunt J, O’Donnell PH, et al. Pembrolizumab (pembro) as first-line therapy for advanced/unresectable or metastatic urothelial cancer: Preliminary results from the phase 2 KEYNOTE-052 study. Ann Oncol. 2016;27(suppl_6): LBA32_PR.
- FDA accepts two sBLAs for Merck’s KEYTRUDA® (pembrolizumab) for locally advanced or metastatic urothelial cancer in cisplatin-ineligible first-line and second-line post-platinum failure treatment settings [news release]. Kenilworth, NJ: Merck; February 3, 2017. http://www.mercknewsroom.com/news-release/oncology-newsroom/fda-accepts-two-sblas-mercks-keytruda-pembrolizumab-locally-advanced-. Accessed April 2017.
- FDA accepts the Biologics License Application for avelumab for the treatment of metastatic urothelial carcinoma for Priority Review. Rockland, MA and New York, NY: EMD Sorono; February 28, 2017. http://media.emdserono.com/2017-02-28-FDA-Accepts-the-Biologics-License-Application-for-Avelumab-for-the-Treatment-of-Metastatic-Urothelial-Carcinoma-for-Priority-Review. Accessed April 2017.
- Apolo AB, Infante JR, Balmanoukian A, et al. Avelumab, an anti-programmed death-ligand 1 antibody, in patients with refractory metastatic urothelial carcinoma: results from a multicenter, phase Ib study. J Clin Oncol. 2017:JCO2016716795. doi: 10.1200/JCO.2016.71.6795