CHICAGO — First-line atezolizumab demonstrated efficacy and appeared tolerable in cisplatin-ineligible patients with metastatic urothelial cancer, according to data from the IMvigor210 phase 2 study presented at the ASCO Annual Meeting.
“This cohort was initially developed as an exploratory cohort to evaluate atezolizumab for cisplatin-ineligible patients with urothelial cancer,” Arjun Vasant Balar, MD, assistant professor of medicine at New York University Langone Medical Center and director of genitourinary medical oncology at the Perlmutter Cancer Center, told HemOnc Today. “The patients evaluated in this study truly reflect the patients we typically see in clinic.”
Arjun Vasant Balar
Many patients with metastatic urothelial cancer are ineligible for first-line cisplatin-based chemotherapy due to renal function or comorbidities, and 30% to 50% do not receive any treatment.
Atezolizumab (Tecentriq, Genentech/Roche) is an anti–PD-L1 immunotherapy being evaluated for various solid tumors. Researchers of the IMvigor210 trial evaluated the efficacy of atezolizumab in two cohorts of patients: those who are receiving the drug as a second-line therapy and those receiving it as upfront treatment because they are not expected to tolerate cisplatin chemotherapy.
Results from the second-line cohort of IMvigor210 prompted the FDA to grant accelerated approval to atezolizumab for the treatment of locally advanced urothelial carcinoma after the failure of platinum-based chemotherapy.
The current analysis includes data from 119 patients (median age, 73 years; 21% aged 80 years or older) of the IMvigor210 trial receiving therapy as first-line treatment.
Patients were eligible for the first-line cohort because they were unable to receive cisplatin due to renal dysfunction, hearing impairment, peripheral neuropathy and ECOG performance status of 2.
Twenty percent of patients had received prior perioperative chemotherapy and 10% previously received radiotherapy. Sixty-six percent had visceral metastases, 70% cleared fewer than 60 mL per minute in a creatinine clearance test, 14% had hearing loss of 25 or more decibels, 6% had prior peripheral neuropathy of grade two or worse, and 20% had an ECOG performance score of 2.
Patients received 1,200 mg of IV atezolizumab every 3 weeks until disease progression by RECIST v1.1 criteria.
The primary efficacy endpoint was confirmed objective response rate by RECIST criteria. Secondary endpoints included duration of response, PFS, OS and safety.
Median follow-up was 14.4 months (range, 0.2-20.1).
ORR for the entire population was 24% (95% CI, 16-32). The complete response rate was 7% and partial response rate was 17%.
Twenty-one out of 28 (75%) responses were ongoing at the time of the data analysis. Median duration of response had not been reached, with the longest ongoing response reaching 18 months.
Median OS was 14.8 months, and 57% of patients achieved 1-year OS.
Researchers then measured PD-L1 expression on tumor-infiltrating immune cells by immunohistochemistry and categorized patients into subgroups with scores of IC0 (n = 39), IC1 (n = 48) and IC2/3 (n = 32).
Patients in the IC2/3 group had the highest ORR rate (28%; 95% CI, 14-47), followed by patients in the IC1 group (23%; 95% CI, 12-37) and IC0 group (21%; 95% CI, 8-36).
Treatment appeared well tolerated. The major of side effects were low grade and only 15% of patients experienced a treatment-related grade 3 or 4 adverse event. The most common toxicities included hypothyroidism, liver function abnormalities, rash and diarrhea. One patient experienced sepsis as a grade 5 treatment-related event.
Six percent of patients withdrew treatment due to an adverse event and 35% experienced dose interruptions.
“We now have evidence that [atezolizumab] could potentially represent a new standard of care,” Balar told HemOnc Today. “This study is promising, but should be interpreted with caution until data from a randomized trial are available. Still, I think nearly all oncologists in the field see [atezolizumab] becoming a standard of care very soon.” – by Nick Andrews
Balar AV, et al. Abstract LBA4500. Presented at: ASCO Annual Meeting; June 3-7, 2016; Chicago.
Disclosure: Balar reports consultant/advisory roles with Cerulean Pharma, Dendreon, Pfizer and Roche/Genentech. Please see the abstract for a list of all other researchers’ financial disclosures.