Tecentriq is showing reduction in tumor size for patients with metastatic urothelial carcinoma, according to a phase 2 study.
Patients with metastatic urothelial carcinoma (mUC) who were ineligible for standard cisplatin-based chemotherapy achieved a 24 percent reduction in tumor size and had a median survival of 14.8 months after taking the immunotherapy agent Tecentriq (atezolizumab), according to phase 2 clinical trial results presented during the 2016 annual meeting of the American Society of Clinical Oncology (ASCO), a gathering of over 30,000 oncology professionals in Chicago.
Tecentriq became the first and thus far only PD-L1 inhibitor to gain approval in mid-May when the FDA authorized its use for patients with locally advanced or mUC whose disease progressed during or after platinum-based chemotherapy, or within 12 months of receiving platinum-containing chemotherapy, either before or after surgery.
At ASCO, lead study author Arjun Vasant Balar, presented data from cohort one of the single-arm IMvigor 210 study, which included 119 patients in the first-line setting who were not candidates for cisplatin therapy.
Cisplatin is the only treatment in mUC that has demonstrated a survival benefit, Balar, who is assistant professor of Medicine at the New York University Langone Medical Center and director of Genitourinary Medical Oncology at the NYU Perlmutter Cancer Center, said during an ASCO presscast.
Balar reported that the objective response rate (ORR) was 24 percent, with 75 percent of these responses still ongoing. The complete response rate was 7 percent, with the partial response rate reported at 17 percent.
Cisplatin ineligibility was defined as one or more of the following factors: impaired kidney function; peripheral neuropathy, or hearing loss grade greater than or equal to two; or ECOG PS2 performance status, which describes a patient’s level of functioning.
Currently, treatment regimens in this setting are heterogeneous and are characterized by short response durations, with many patients managed with best supportive care only.
“I would underscore the importance of this study because it is looking at cisplatin-ineligible patients as opposed to carboplatin-treated patients,” said Charles Ryan, professor of Clinical Medicine and Urology and Program Leader, Genitourinary Medical Oncology, at the UCSF Helen Diller Family Comprehensive Cancer Center. “It is a substantial patient population in bladder cancer. There are many patients who are cisplatin-ineligible,” continued Ryan, who served as an ASCO expert during the presscast.
Patients in cohort one had a median age of 73 years, and 21 percent were 80 years and older. Eighteen percent reported prior systemic therapy, 10 percent had received radiotherapy and 66 percent reported visceral metastases. “We observed that response was seen in all subgroups including complete response [CR] in all subgroups, and this was at a median follow up of 14.4 months,” said Balar.
Tecentriq was generally well tolerated. The investigators reported 6 percent of patients withdrawing from the study because of adverse effects (AEs). Most AEs were grade one or two; there was one case of a grade five AE. Thirty-five percent of patients experienced an AE that led to dose interruption.
In comparison to real world studies and clinical trials, Tecentriq compared favorably with historic data involving cisplatin-ineligible patients, reported the researchers.
IMvigor 210 included two groups of patients: those receiving Tecentriq as a second-line therapy and those receiving Tecentriq as an upfront treatment. The researchers have previously reported results from the second-line therapy group. Based on those results, the FDA granted Tecentriq an accelerated approval in second-line and later settings. The approval was based on data in which Tecentriq had an ORR of 14.8 percent in patients with locally advanced or mUC, regardless of PD-L1 expression.
“Currently, the FDA label indicates that Tecentriq should be used in patients who have progressed on prior platinum-based chemotherapy, which includes carboplatin- and cisplatin-based treatment. The indication is agnostic to the type of platinum,” said Balar.
The findings presented at ASCO would suggest a first-line setting for the agent in the future.
“My study, which looked at cohort one, is really an exploratory cohort. The survival data are very provocative, but the data are still immature. I do think there is a benefit there, but until we have comparative data, it is going to be difficult to compare with chemotherapy,” said Balar.
However, Balar was cautiously optimistic. “Do I envision a time when PD-1 or PD-L1 targeted therapy in the frontline setting is possible? Yes, absolutely. I think that is where the field is going. We just need the trials to show it.” His sentiments were echoed by Ryan. “I think it is safe to envision a future in which PD-L1 therapy could be used in the front line, but we do need to do those confirmatory studies.”
IMvigor210 is the first trial to test the efficacy of Tecentriq as the initial treatment in patients with advanced bladder cancer. These data are encouraging, and the researchers are planning a randomized phase 3 trial of Tecentriq as an upfront treatment for advanced bladder cancer, according to an ASCO press release. A randomized clinical trial of Tecentriq as an adjuvant treatment for early-stage bladder cancer is also underway.
Meanwhile, there are several ongoing clinical trials exploring other immune checkpoint inhibitors, including Opdivo (nivolumab), Keytruda (pembrolizumab) and durvalumab in localized and advanced bladder cancer.