ASCO 2024 Meeting Report — Genitourinary Cancers

The 2024 American Society of Clinical Oncology (ASCO) annual meeting, held May 30 to June 3 in Chicago, highlighted important advances in treatment across a broad spectrum of malignancies. Here, NEJM Journal Watch Oncology and Hematology Associate Editor Robert Dreicer, MD, MS, MACP, FASCO, reviews key trials in GU cancers.

In patients with locally advanced or metastatic urothelial cancer, treatment with enfortumab vedotin improves progression-free survival (PFS) and overall survival (OS) at all levels of exposure, compared with chemotherapy, according to an industry-supported pharmacokinetics analysis.

Researchers examined data from the EV-101, EV-201, and EV-301 trials of enfortumab vedotin in urothelial cancer. Dose modifications to manage adverse events — including reductions to 1.0 mg/kg or 0.75 mg/kg on days 1, 8, and 15 of each 28-day cycle — were common.

In EV-301 in particular, where the starting dose was 1.25 mg/kg, 35% of patients dropped to 1.0 mg/kg and 11% dropped to 0.75 mg/kg. Exposure ranged from a median absolute dose intensity of 2.37 mg/kg over 4 weeks in the lowest quartile to 3.59 mg/kg over 4 weeks in the highest. PFS and OS were longer at all quartiles of enfortumab vedotin exposure, compared with chemotherapy. For example, median PFS was 4.44 months in the lowest quartile and 5.65 in the highest quartile, versus 3.71 months with chemotherapy, and median OS was 11.0 and 12.6 months, respectively, versus 8.97 months with chemotherapy.

Overall, lower enfortumab vedotin exposure was associated with lower risk of adverse events, including grade 3 or higher rash or skin reactions, grade 2 or higher peripheral neuropathy, and grade 3 or higher hyperglycemia.

Summary by Amy Herman, Staff Writer

COMMENT — Dr. Robert Dreicer

Among the challenges of administering the recently FDA-approved enfortumab vedotin/pembrolizumab combination is gauging the impact of the relatively frequent need for dose modification of enfortumab vedotin. This analysis provides support to clinicians and patients that enfortumab vedotin modification will likely not affect the regimen's efficacy.

Read more about the study.

Additional treatment with chemohormonal therapy prolongs progression-free survival (PFS) in patients who develop castration-resistant prostate cancer after early chemohormonal therapy for metastatic, hormone-sensitive prostate cancer, according to findings from CHAARTED2, a phase 2, partially industry-funded, prospective, open-label trial.

Some 220 patients with metastatic, castration-resistant prostate cancer who previously received androgen-deprivation therapy (ADT) plus docetaxel in the castrate-sensitive setting were randomized to receive a combination of abiraterone/prednisone plus cabazitaxel (up to 6 cycles) or abiraterone/prednisone alone.

During a median 4 years' follow-up, PFS, the primary end point, was longer in the cabazitaxel-plus-abiraterone/prednisone group — a median of 14.9 months, versus 9.9 months in the abiraterone/prednisone-alone group. Time to prostate-specific antigen (PSA) progression, a secondary end point, was also longer in the combination group — a median of 10.0 months versus 6.1 months. An interim analysis showed no difference in overall survival.

Summary by Christine Judge, Staff Writer

COMMENT — Dr. Robert Dreicer

Although too many patients still do not receive ADT intensification in the castrate-sensitive metastatic setting, most who do receive either abiraterone/apalutamide/enzalutamide or darolutamide with or without docetaxel; thus, while important, this study's findings have little clinical application today.

Read more about the study.