177Lu-PSMA-617 in Metastatic Castration-Resistant Prostate Cancer: A Review of the Evidence and Implications for Canadian Clinical Practice.

Prostate-specific membrane antigen (PSMA) is highly expressed in prostate cancer and a therapeutic target. Lutetium-177 (177Lu)-PSMA-617 is the first radioligand therapy to be approved in Canada for use in patients with metastatic castration-resistant prostate cancer (mCRPC). As this treatment represents a new therapeutic class, guidance regarding how to integrate it into clinical practice is needed. This article aims to review the evidence from prospective phase 2 and 3 clinical trials and meta-analyses of observational studies on the use of 177Lu-PSMA-617 in prostate cancer and discuss how Canadian clinicians might best apply these data in practice. The selection of appropriate patients, the practicalities of treatment administration, including necessary facilities for treatment procedures, the assessment of treatment response, and the management of adverse events are considered. Survival benefits were observed in clinical trials of 177Lu-PSMA-617 in patients with progressive, PSMA-positive mCRPC who were pretreated with androgen receptor pathway inhibitors and taxanes, as well as in taxane-naïve patients. However, the results of ongoing trials are awaited to clarify questions regarding the optimal sequencing of 177Lu-PSMA-617 with other therapies, as well as the implications of predictive biomarkers, personalized dosimetry, and combinations with other therapies.

Addressing controversial areas in the management of advanced prostate cancer in Canada Areas of consensus and controversy from the third Canadian consensus forum.

INTRODUCTION: The management of prostate cancer (PCa) is rapidly evolving. Treatment and diagnostic options grow annually, however, high-level evidence for the use of new therapeutics and diagnostics is lacking. In November 2022, the Genitourinary Research Consortium held its 3rd Canadian Consensus Forum (CCF3) to provide guidance on key controversial areas for management of PCa. METHODS: A steering committee of eight multidisciplinary physicians identified topics for discussion and adapted questions from the Advanced Prostate Cancer Consensus Conference 2022 for CCF3. Questions focused on management of metastatic castration-sensitive prostate cancer (mCSPC); use of novel imaging, germline testing, and genomic profiling; and areas of non-consensus from CCF2. Fifty-eight questions were voted on during a live forum, with threshold for "consensus agreement" set at 75%. RESULTS: The voting panel consisted of 26 physicians: 13 urologists/uro-oncologists, nine medical oncologists, and four radiation oncologists. Consensus was reached for 32 of 58 questions (one ad-hoc). Consensus was seen in the use of local treatment, to not use metastasis-directed therapy for low-volume mCSPC, and to use triplet therapy for synchronous high-volume mCSPC (low prostate-specific antigen). Consensus was also reached on sufficiency of conventional imaging to manage disease, use of germline testing and genomic profiling for metastatic disease, and poly (ADP-ribose) polymerase (PARP) inhibitors for BRCA-positive prostate cancer. CONCLUSIONS: CCF3 identified consensus agreement and provides guidance on >30 practice scenarios related to management of PCa and nine areas of controversy, which represent opportunities for research and education to improve patient care. Consensus initiatives provide valuable guidance on areas of controversy as clinicians await high-level evidence.

Nivolumab in Squamous Cell Carcinomas of the Head and Neck (SCCHN): A Real-world Outcome Study in Ontario, Canada.

The CheckMate-141 trial led to the approval of nivolumab in platinum-resistant metastatic/advanced squamous cell carcinomas of the head and neck (SCCHN). We evaluated the outcomes of SCCHN patients in Ontario, Canada, treated with nivolumab through retrospective review of the provincial treatment registry. Kaplan-Meier method was used to estimate overall survival (OS) and Cox regression to evaluate the prognostic effect of selected factors. Nivolumab was used as second-line therapy after disease relapse for curative-intent platinum chemotherapy (PC) (indication 1-I1), as second-line therapy post-PC in noncurative intent (indication 2-I2), and as first-line therapy in noncurative intent due to contraindication for PC (indication 3-I3). The median OS for patients treated with nivolumab was 5.8 months (95% CI: 4.5-7.3), and the 1-year OS was 28.4% (CI: 2.10-36.1). When patients with I3 were excluded to match inclusion criteria for CheckMate-141, median OS was 4.8 months (CI: 3.6-6.7) with 1-year OS of 21.8% (14.4-30.1). Patients with lower body surface area (BSA) (<1.81) had a median OS of 3.9 months (CI: 3.1-6.7) versus 9.0 months (CI: 6.5-14.8) in those with higher BSA, hazard ratio (HR)=0.12 (CI: 0.04-0.39, P <0.001). Patients receiving nivolumab for I1 had a median OS of 7.2 months (CI 3.8-9.8) versus 11.9 months (CI: 6.2-not reached) for I3, HR=1.73 (CI: 0.94-3.16). Patients receiving nivolumab for I2 had a median OS of 3.9 months (CI: 2.9-5.4) as compared with I3, HR=3.27 (CI: 1.80-5.94). Real-world analysis of patients with advanced/metastatic SCCHN in Ontario, Canada, treated with nivolumab demonstrates poorer median OS compared with CheckMate-141 trial. Lower BSA was a predictor of poorer median OS.