With help from DNA testing company Natera and its personalized molecular residual disease (MRD) blood test Signatera, Roche’s PD-L1 inhibitor Tecentriq has secured its 11th indication in the US with a new bladder cancer approval.
As confirmed by Signatera, Tecentriq and subcutaneous Tecentriq Hybreza are now available as adjunctive treatments for adult patients with muscle-invasive bladder cancer (MIBC) who have circulating tumor DNA molecule residual disease (ctDNA MRD) after cystectomy.
“By combining our cancer immunotherapy Tecentriq with state-of-the-art MRD testing, we will be able to more accurately identify patients who are candidates for intervention and those who can safely avoid unnecessary treatment,” Levi Garraway, MD, Roche’s chief medical officer and head of global product development, said in a company release. “We look forward to bringing this first-of-its-kind ctDNA-based regulatory approval to bladder cancer physicians and patients in the United States.”
Roche says that surgery to remove the bladder (cystectomy) in combination with chemotherapy is typically used as the main standard of care for patients diagnosed with MIBC, but of the more than 150,000 patients worldwide who undergo this procedure each year, nearly half experience a recurrence of their cancer after surgery.
Doctors typically rely on tumor staging to determine whether a patient needs post-surgical treatment, but Natera’s Signatera assay can find molecular evidence of cancer in the blood before the cancer is visible on standard imaging tests.
This first FDA approval of a ctDNA-guided therapy will allow clinicians to selectively provide treatment to patients who are at highest risk for disease recurrence and would benefit most from immunotherapy, reducing post-surgery anxiety and allowing many people to safely avoid further treatment, Merrimargaret Deudes, CEO of the Bladder Cancer Advocacy Network, explained in a Roche release.
The FDA simultaneously approved both Tecentriq and the companion diagnostic Signaterra after reviewing data from Roche’s late-stage IMvigor011 trial. This study was the first prospective phase 3 study to significantly improve survival in MIBC with a ctDNA-based approach.
After 761 prospective trial participants underwent serial ctDNA testing for at least one year postoperatively, 250 were evaluated for either Tecentriq or placebo.
In 250 patients who were deemed eligible for the treatment phase of the trial based on the assay, Tecentriq reduced the risk of disease recurrence or death by 36%, and specifically the risk of death by 41%.
The study results suggest that the combination of treatment and diagnosis “has the potential to change the way resectable bladder cancer is managed for the tens of thousands of patients diagnosed with MIBC each year,” Alexei Aleshin, MD, Natera’s chief medical officer and general manager of oncology, said at the time.
Roche had switched Tecentriq’s strategy in MIBC in 2020 after the study’s predecessor, IMvigor010, failed to meet its primary goal of disease-free survival in an unselected group of MIBC patients. Now, the company says Natera’s ctDNA-guided therapy, which it helped introduce, is being studied in other types of cancer.
Tecentriq’s latest approval has precision medicine aspects that may offer unique advantages in the crowded bladder cancer treatment landscape. Tecentriq itself was approved first-in-class in 2016 to treat certain patients with urothelial carcinoma, a common type of bladder cancer, making it the first PD-L1 inhibitor to open the door in this disease area. Since then, the drug has expanded its indications to different types of cancer, including breast and lung cancer.
Meanwhile, other PD-L1 inhibitors are also making great progress in the field of bladder cancer. AstraZeneca’s Imfinzi became the first immunotherapy to win a perioperative label in MIBC last year, and Bristol-Myers Squibb’s Opdivo won postoperative approval in 2021. Additionally, the combination of Merck’s flagship drug PD-L1 Keytruda and Pfizer’s antibody-drug conjugate Padcef has performed well recently, winning multiple clinical trials in a variety of bladder cancers. population.
