Abstract 4506 was a single arm, phase II study analyzing two cycles of Atezolizumab prior to radical cystectomy among patients with T2-4N0M0 transitional cell carcinoma. The primary endpoints included pathological complete response occurring in ≥20% of patients, and increase in CD8 count. Adverse events were assessed as well. Overall, there were 74 patients receiving Atezolizumab, and 67 underwent subsequent radical cystectomy. The results demonstrated that almost 30% of the patients had pathological complete response (T0 disease), 40% were PD-L1 positive patients, and 16% were PD-L1 negative patients.
The most common related adverse event was fatigue (21%) and the most common grade 3 or 4 adverse event was transaminitis (4%). In general, grade 3 or 4 complications occurred in 10% of patients undergoing radical cystectomy, with no post-operative deaths. This study demonstrated that Atezolizumab*2 cycles is a safe treatment prior to cystectomy in ineligible patients for cisplatin based chemotherapy. Pathological response rate was ~30%, and disease progression was less common in this treatment strategy. Long term follow-up is mandatory to fully understand the effect of this treatment.
Abstract 4507 was a phase 2 PURE-01 trial assessing pembrolizumab prior to radical cystectomy for MIBC. This is an open-label, single-arm, phase 2 study. Its goal was to evaluate the activity, medical and surgical safety, and immune modulatory effects of pembrolizumab given prior to radical cystectomy. Pembrolizumab was administered at the dose of 200mg, as a 30-minute IV infusion, every 3 weeks for a total of three cycles prior to radical cystectomy. The primary outcome was pathologic complete response (pT0) at the time of radical cystectomy, with a median follow-up for of 8 months. Overall, 43 patients were enrolled up to the abstract presentation. A total of 17/43 patients were pT0 (39.5%, 95%CI: 26.3-54.4) after cystectomy, and 5 patients were.
Lastly, abstract 4508 was discussed. This was a randomized phase 2 study of TIP vs. BEP in intermediate- and poor-risk germ cell tumor (GCT) patients, conducted across 7 centers. Patients were randomized to 4 cycles of TIP (paclitaxel 120mg/m2 days 1-2; ifosfamide 1200mg/m2 days 1-5; and cisplatin 20mg/m2 days 1-5) or standard BEP. The primary endpoint was the 6-month favorable response rate, and the secondary endpoints included progression free survival (PFS) and overall survival (OS). Of the 91 analyzed patients (n = 45 TIP, n = 46 BEP), 37 had intermediate-risk and 54 had poor-risk disease. In the abstract presentation, 86 patients (TIP: n = 42; BEP; n = 44) were available for evaluation for a 6-month favorable response, showing no difference demonstrated between the two arms (76% for TIP vs. 73% for BEP). The median follow-up time was 1.71 years. Laboratory and gastrointestinal toxicities were worse for TIP, whereas infections and respiratory toxicities were worse for BEP. In this negative, but important study, the authors concluded that first-line TIP did not improve the 6-month rate of favorable response when compared to BEP in patients with poor- or intermediate-risk GCT. However, this study did demonstrate that TIP could be an alternative to BEP for patients with a contraindication to bleomycin. Most importantly, it seems we have reached the “ceiling” with 1st line chemotherapy for patients with intermediate- and poor- risk GCT, and we need to change this.
Presented by: Dr. Matthew Galsky, Icahn school of medicine at Mount Sinai, New York, USA
Written by: Hanan Goldberg, MD, Urologic Oncology Fellow (SUO), University of Toronto, Princess Margaret Cancer Centre, Twitter:@GoldbergHanan at the 2018 ASCO Annual Meeting - June 1-5, 2018 – Chicago, IL USA