Top Takeaways from ASCO: Urothelial Cancer

Engineered immunotherapy, petrolizumab impact PFS rates in patients.

Issue: August 10, 2015

CHICAGO — Data on two immune checkpoint inhibitors for the treatment of urothelial cancer represent important findings for this type of cancer presented at the ASCO 2015 Annual Meeting, according to physicians who discussed the Top Takeaways from the conference with Healio.com.

Study results

Atezolizumab and urothelial bladder cancer

Atezolizumab (MPDL3280A), an anti-PDL1 antibody-blocking agent binding to PD-1 and B7.1 receptors, induced some rapid and durable responses and was well-tolerated in a cohort of patients with previously treated, metastatic urothelial bladder cancer (UBC).

Patients with previously treated, metastatic UBC were enrolled in an expansion cohort and assigned to receive either 15 mg/kg or 1,200 mg IV MPDL3280A every 3 weeks. Updated analyses presented during this oral abstract session include 87 efficacy-evaluable, selectively enrolled UBC patients; 46 were PD-L1 IHC 2/3 and 41 were IHC 0/1.

Overall response rates were 50% (95% CI 35-65%, with 20% CR and 30% PR) for immunohistochemistry (IHC) 2/3 patients and 17% (95% CI 7-32%, with 17% PR) for IHC 0/1 patients. Median response duration has not been reached yet in either IHC group (range 0-43 months). Median time to response was 2 months. Median PFS was 6 months (0-18) for IHC 2/3 patients and 1 month (0-14) for IHC 0/1 patients. Median OS rates at 1 year were 57% (95% CI 41-73%) for IHC 2/3 patients and 38% (95% CI 19-56%) for IHC 0/1 patients.

Response, PFS and OS data was described as “very promising as compared to historical controls.” In addition, response rates correlated with tumor and blood-based biomarkers.

Biomarker analysis from KEYNOTE-012

Updated data for pembrolizumab, an anti–PD-1 antibody, demonstrated anti-tumor activity and safety in patients with recurrent or metastatic PD-L1–positive urothelial cancer.

Patients with recurrent, metastatic or persistent cancer of the bladder, renal pelvis, ureter or urethra were treated with pembrolizumab 10 mg/kg every 2 weeks until the patients achieved a complete response, progression or unacceptable toxicity. Thirty-three patients with a median age of 70 years were followed for a median of 15 (0.6-20) months; 33% of these patients had been treated with three or more prior therapies.

Anti-tumor activity was described as significant. ORR was 28% (95% CI 13-47), with 3 (10%) complete and 5 (17%) partial responses per review. The median time to response was 9 (8-56) weeks. The 12-month PFS rate was 19% and the 12-month OS rate was 53%.

Petros Grivas

Top takeaways from the data

Petros Grivas , MD, PhD, a medical oncologist at the Cleveland Clinic, calls the data from these trials very promising and compelling and says the response rates in these trials compare favorably to historical controls and certainly support the ongoing investigation in larger trials.

“The traditional historical numbers with response rates in this second-line metastatic disease setting are very low — around 10% to15%,” Grivas said. “The results from the larger subsequent ongoing trials will be awaited with enthusiasm. There is high likelihood that, in the future, we may be able to add tremendous new tools in our armamentarium and utilize immunotherapy to improve patient outcomes.”

Arjun V. Balar

Arjun V. Balar , MD, a medical oncologist and Director of Genitourinary Medical Oncology at the NYU Perlmutter Cancer Center, noted a “tremendous amount of excitement” about the novel immune checkpoint inhibitors being tested in advanced bladder cancer, specifically anti-PD-L1 and PD-1 antibodies.

“The data presented ... shows that, in terms of the long-term data that was presented from two phase 1 trials of PD-L1 and PD-1 antibodies, therapy is extremely well-tolerated and a proportion of patients have significant and durable responses,” Balar said.

Grivas agreed, noting a “transforming era” for bladder cancer treatment.

“There have been no FDA-approved therapies in the second-line treatment of bladder cancer in the metastatic setting,” Grivas said. “All of us were excited about these data and we are working on accruing patients in the larger trials that are available.”

He notes “there are some things we have to keep in mind” when looking at the promising results of these trials.

“The first one is patient selection,” Grivas said. “There’s a discussion about the optimal biomarker in this disease. PD-L1 expression by immunohistochemistry has some predictive utility, but it is not perfect and is not the whole story. I think we have to work very hard and utilize biology and immunology in order to find more biomarkers to better select patients who might benefit from these treatments and spare potential side effects to the others.”

However, both physicians believe the results of these initial trials are encouraging.

“I have to say that I’m impressed with the relatively low toxicity profile and high tolerance of these compounds in the phase 1 studies,” Grivas said, adding that data from ongoing phase 2 studies should become available in time for ASH 2015 or ASCO 2016.

Balar said these trials have “the potential to be practice-changing, as some of these new treatments are now being rolled out into phase 2 and phase 3 clinical trials.” – by Julia Ernst, MS

References:

Petrylak DP, et al. Abstract 4501. Presented at: ASCO Annual Meeting; May 29-June 2, 2015; Chicago.

Plimack ER, et al. Abstract 4502. Presented at: ASCO Annual Meeting; May 29-June 2, 2015; Chicago.