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At this year's meeting of the American Society of Clinical Oncology (ASCO 2020), held virtually May 29–31, investigators discussed the latest findings in cancer research. Associate Editor Robert Dreicer, MD, MS, MACP, FASCO, reviewed key presentations on new genitourinary cancer therapies. All meeting abstracts can be viewed in the ASCO meeting library.
Management options for patients with advanced urothelial cancer have improved since the introduction of checkpoint inhibitors as second-line therapy following platinum-based chemotherapy. However, only a relatively small subset of patients respond to these agents.
To test the effectiveness of the PD-L1 inhibitor avelumab in this setting, Powles and colleagues conducted an industry-sponsored, randomized, phase III trial (JAVELIN Bladder 100; abstract LBA1) involving 700 patients with metastatic urothelial cancer whose response to four to six cycles of platinum multiagent chemotherapy was stable disease or better. Patients were assigned to avelumab plus best supportive care (BSC) or BSC alone. The median age of patients was 68 and 69, respectively; 54% and 48% were PD-L1+; and 55% had visceral metastases.
Overall survival (the primary endpoint) was significantly longer with avelumab plus BSC than with BSC alone in all patients (21.4 vs. 14.3 months; hazard ratio, 0.69; P<0.001) as well as in PD-L1+ patients (not reached vs. 17.1 months; HR, 0.56; P<0.001). Among all patients, subsequent anticancer therapy was received by fewer patients in the avelumab arm (42.3% vs. 61.7%). There were no new safety signals for avelumab.
This important trial demonstrates a survival benefit with the use of “switch maintenance” — with a checkpoint inhibitor following first-line chemotherapy — that will likely become a standard of care following FDA approval. Additional studies testing chemotherapy/checkpoint-inhibitor combinations and chemotherapy/immunotherapy combinations will likely be reported over the next 12 months.
Over the past several years, a number of new agents have been approved for men with metastatic castration-resistant prostate cancer (mCRPC). However, the need for new therapy options remains. LuPSMA (177Lu-PSMA-617) is a radiolabeled small molecule that binds to prostate-specific membrane antigen (PSMA), which is expressed on the tumor cell surface of most patients with advanced prostate cancer. Prior phase II studies have established that this agent has significant clinical activity in mCRPC and is reasonably safe.
Hofman and colleagues conducted a randomized, phase II study of LuPSMA in men with mCRPC who had received prior docetaxel (abstract 5500). Patients were randomized to receive either LuPSMA every 6 weeks (up to 6 cycles) or cabazitaxel every 3 weeks (up to 10 cycles). Of the 200 patients randomized, the median age was 72, most had ECOG performance status of 0 or 1, and the median PSA at entry was 100 ng/mL in the cabazitaxel arm and 94 ng/mL in the LuPSMA arm. The primary endpoint was a ≥50% reduction in PSA. Patients were required to have progressive disease, PSMA PET+ disease, and no 18F-fluorodeoxyglucose (FDG)+/PSMA− disease sites.
The response rate was higher with LuPSMA than with cabazitaxel (66% vs. 37%; P=0.001). In a preliminary analysis, PSA progression-free survival seemed to also favor LuPSMA. Toxicities of both agents were consistent with prior reports
This study adds to the body of evidence that 177Lu-PSMA-617 is active in patients with mCRPC. However, only limited conclusions can be drawn, since the endpoint reached, although of interest, has no long-term clinical relevance. The results of the phase III Vision study conducted as a registration study are awaited with considerable interest.