Introduction and objective
PURE-01 trial provided several activity signals mainly represented by pathological response endpoints. We aimed to report updated results on recurrence-free survival (RFS) and overall survival (OS) at longer follow-up.
Methods
From 02/2017 to 06/2020, 136 patients were treated. RFS was defined as the time from first pembrolizumab dose to either: i) radiological progression, ii) local or distant recurrence, iii) death from any cause. Statistical analyses consisted of Kaplan-Meier analyses and Cox regression models.
Results
Of all 136 patients, 120 (88%) were males and median age was 68 years (IQR 62-74), while 76 patients (56%) exhibited a PD-L1 CPS≥10% on the TURB specimen pre-therapy. At radical cystectomy pathology, 57 (42%), 25 (18%), 34 (25%) and 20 (15%) patients harbored respectively ypT0N0, ypT1/a/isN0, ypT2-4N0 and ypTanyN+ disease. Finally, 9 patients (7%) received also adjuvant chemotherapy: 3 ypT2-4N0 and 6 ypTanyN+ patients. After a median follow-up of 27 months (IQR 21-38), 22 patients (16%) experienced a recurrence, while 14 patients (10%) died. At Kaplan-Meier curves (Figure 1), patients treated with neoadjuvant pembrolizumab exhibited a 36-month OS of 95%, 86%, 93% and 56% for respectively ypT0N0, ypT1/a/isN0, ypT2-4N0 and ypTanyN+ stages. Similarly, they exhibited a 36-month RFS of 94%, 96%, 67% and 44% for respectively ypT0N0, ypT1/a/isN0, ypT2-4N0 and ypTanyN+ stages. In ITT population, 36-month RFS and OS for CPS≥10% vs CPS>10 cohorts were respectively 88% vs 72% and 91% vs 79%. At multivariable Cox regression analyses, only age (HR 1.1, p=0.02) and ypTanyN+ stage (HR 9.0, p=0.02) represented independent predictors of overall mortality, after adjustment for stage, CPS ≥10% and adjuvant chemotherapy. Similarly, when recurrence represented the outcome, only ypT2-4N0 (HR 8.6, p=0.007) and ypTanyN+ (HR 15.9, p=0.001) stages represented independent predictors.
Conclusions
Pembrolizumab followed by radical cystectomy confirms to be an effective treatment for patients with MIBC, unselected for biomarkers and for cisplatin eligibility. This data should be tested towards the data emerging in adjuvant setting and in light of the ongoing randomized perioperative phase 3 trials.
Source of funding
NA