Atezolizumab: Soon to Be a Monotherapy?

Although the current first-line standard for the treatment of bladder cancer is cisplatin-and has been since the 1970s-a newly approved drug may prove to usurp cisplatin’s place in the treatment paradigm for certain patients. According to new research presented June 5 at the American Society of Clinical Oncology (ASCO) annual meeting in Chicago, IL, checkpoint inhibitor Tecentriq (atezolizumab) from Roche shrank tumors of patients with advanced bladder cancer by at least 30% and stalled tumor growth in 28 of 119 (or 24% of) patients. Of the 28 patients who initially responded to treatment, 21 patients remain on therapy and are still in remission, while the other seven patients had their cancer return and were given alternative treatments. Half of the 28 patients who responded to treatment did so within 15 weeks after treatment initiation.

Average survival of patients in the atezolizumab trial was approximately 14.8 months, which was “comparable, if not better, than what we typically see with chemotherapy,” noted lead investigator Arjun Balar, MD, assistant professor at NYU Langone Medical Center, in a video produced by NYU. Compared with chemotherapy, patients tolerated treatment with atezolizumab well, Balar added, and many of the patients experienced no side effects whatsoever.

FDA approved Tecentriq on May 18, 2016, but as a second-line treatment for patients who have failed to improve after receiving platinum-based chemotherapy. The new study suggests that Tecentriq may be a good candidate for first-line status, as all of the patients in the trial received atezolizumab as an initial therapy (i.e., not following platinum-based chemotherapy).

Many patients are prevented from using cisplatin as a first defense, as kidney and nerve damage are major concerns.  Hearing loss, nausea and vomiting, and other toxicity issues can also be major concerns, especially for elderly patients. For patients who are ineligible to start a cisplatin regimen, atezolizumab may be a good first-line option, the authors emphasized.

Although the atezolizumab’s true mechanism of action is still not totally known, it is believed that the drug inhibits the binding of programmed death ligand-1 (PD-L1). Merck is testing anti-PD-L1 drug avelumab in clinical trials for the treatment of bladder cancer, which may serve as a main competitor to atezolizumab. Additionally, Merck is testing Keytruda (pembrolizumab) and Bristol-Myers Squibb is testing Opdivo (nivolumab) in certain bladder cancer patients who exhibit checkpoint inhibitor biomarkers, so both of these drugs could also serve as competitors-although both of these drugs both bind directly to PD-1, not to PD-LI. Nevertheless, all of the aforementioned candidates prevent the formation of the PD-1/PD-L1 receptor/ligand complex and allow immune cells to work freely without being blocked by cancer cells.

Source: NYU Langone Medical Center