As a discussant at the American Society of Clinical Oncology virtual meeting, Shilpa Gupta, MD, a genitourinary oncologist from the Cleveland Clinic in Ohio, provided an assessment of new trials testing the role of perioperative immunotherapy in urothelial cancer.
In this exclusive MedPage Today video, Dr. Gupta breaks down the data from two abstracts on muscle-invasive bladder cancer presented at the meeting.
Following is a transcript of her remarks:
[GU14-188] was a phase II neoadjuvant study of gemcitabine [Gemzar] and pembrolizumab [Keytruda] in muscle-invasive bladder cancer patients who were cisplatin ineligible. Thirty-seven patients were enrolled on this trial and the primary endpoint was pathologic downstaging rates to pT1N0 or below. Patients received five doses of gemcitabine and pembrolizumab, and the key eligibility criteria was cisplatin ineligibility. About 56% of patients had CT3/T4 disease and 43% of patients had CT2 disease. So that was the patient characteristics. The main reason for cisplatin ineligibility was renal impairment and hearing loss.
The patients got all the doses that were intended for pembrolizumab and gemcitabine. And as far as treatment-related adverse events go, patients did not have any grade 5 treatment-related adverse events, but about 36% of patients had grade 3/4 non-heme treatment-related adverse events and 44% of patients had grade 3/4 heme-related adverse events. Notably, the surgery was not withheld in anybody due to the toxicity. And the median time to radical cystectomy was 5.6 weeks from the last treatment; 51% of patients had pathologic downstaging and the study met its primary endpoint. Forty-five percent of patients had complete responses at surgery. The relapse-free survival at 12 months was 67%, and the overall survival at 12 months was 88%.
Overall, this regimen was found to be effective, feasible, and with manageable toxicity. And in this patient population, it is imperative that we are not delaying the curative procedure of cystectomy, and this study showed that everybody got cystectomy at a median of 5.6 weeks from the last treatment. So these results are very exciting and provide us reassurance that immunotherapy can be built upon as a backbone in cisplatin-eligible muscle-invasive bladder cancer patients.
This [next study] was the NABUCCO trial, and Dr. van Dijk and colleagues presented the biomarker analysis and updated clinical follow-up. So in this study, 24 high-risk stage III urothelial cancer patients were enrolled — that is, patients could have clinical T3-T4aN0 or clinical T2-T4aN1-3 urothelial carcinoma. And these patients were cisplatin-ineligible or refused chemotherapy.
The treatment was with one dose of ipilimumab [Yervoy], followed by a dose of ipilimumab and nivolumab [Opdivo], followed by a dose of nivolumab prior to surgery. The primary endpoint in this case was feasibility, that is patients making it to surgery within 12 weeks. And secondary endpoints for efficacy and biomarker analysis and safety.
Initially at ESMO 2019, the authors have reported complete response rates in 46% of patients. And that there was a positive correlation seen with high PD-L1 expression. And now the authors report that at a median follow-up of 15.9 months, the relapse-free survival was 92%, as well as the overall survival.
They did some really interesting biomarker analyses for the study. They found that high tumor mutational burden correlated with the complete responses. They also showed that TGF-beta emerged as a biomarker of resistance, that is high levels of TGF-beta correlated with non-response or resistance. The responses appeared irrespective of baseline CD8 T-cell immunity. And the authors also did a novel biomarker looking at tertiary lymphoid structure dynamics, and they showed that the full change in the tertiary infrastructure maturation correlated with higher complete responses.
Overall, this study again, sets the pace that immunotherapy is feasible and effective in a neoadjuvant setting in cisplatin-ineligible patients, and does not result in a significant number of patients not being able to get cystectomy, or any delays to cystectomy. This is exciting data, and ongoing and future trials will set a new treatment paradigm, hopefully.
Source: MedicalNewsToday.com
