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Genitourinary cancer abstracts to watch at ASCO Annual Meeting
Donald L. “Skip” Trump, MD, FACP, CEO and executive director of Inova Schar Cancer Institute and HemOnc Today’s associate editor for medical oncology, identified several genitourinary cancer abstracts to watch at ASCO Annual Meeting.
Below, he provides an overview of each study and explains why the results could be important for clinical practice.
Prostate cancer
Abstract 5076 — This is an evaluation of polymorphisms in the molecule transport protein SLCO2B1, variant alleles of which have been shown in preclinical investigations to be associated with variations in tissue levels of abiraterone. SLCO2B1 concentrates abiraterone in tumor tissue and in the prostate. Conceptually, polymorphisms in these proteins could vary the efficacy of transport and hence tumor content and activity of abiraterone; polymorphisms could be associated with differences in the effectiveness of abiraterone.
In a series of patients from a University of Utah registry of men with prostate cancer, 401 men who received abiraterone were genotyped for SLCO2B1 polymorphisms. Of these, 80% were wild type homozygous for rs12422149, 1% were homozygous for a variant and 18.5% were heterozygous. Men who were heterozygous for this variant achieved significantly improved median PFS compared with the homozygous group (8.9 months vs. 6.3 months; HR = 0.46; 95% CI, 0.23-0.94).
My interest in this abstract is that it lays additional groundwork for ‘personalizing’ the use of molecules that disrupt androgen signaling. These and other studies that characterize the variants in these signaling pathways (ARv7 in circulating tumor cells) may allow us to better characterize those populations most likely to benefit. Among populations less likely to benefit, we could consider abandoning that drug sooner or not using it all.
Abstract 5082 — This is a study of 22 men with high-risk prostate cancer for whom radical prostatectomy was planned and who received goserelin plus enzalutamide (Xtandi; Astellas, Pfizer) for 6 months prior to prostatectomy. The question posed was: What effect does this potent approach to androgen deprivation have in the prostate?
The changes were striking and very encouraging with regard to use of this more potent approach to androgen deprivation. Among 22 patients with high-risk disease, no patient had any sign of progression on repeat MRI or PSA measurement. Almost 80% showed reduction in tumor and 20% were unchanged. In four of the 22 patients, little or no cancer was found when the prostate was removed at the time of surgery.
This indicates that — in as many as 20% of men with poor prognosis, clinically localized prostate cancer — remarkable tumor reduction can be obtained with potent neoadjuvant androgen deprivation. This is another indication for how we might consider using these powerful approaches to androgen deprivation in early-stage disease.
Kidney cancer
Abstract 4515 — This study struck me from a conceptual standpoint. Researchers looked at RNA expression profiles in the tumor and microenvironment of the tumor — immune cells and blood vessels — in more than 400 patients. They were able to characterize four distinct molecular subtypes of renal cell carcinoma associated with different outcomes in therapy using RNA profiling in both the tumor and the stroma. This is a large study with a new analytic technology applied to kidney cancer, which suggests that we may be able to define tumor, immune and angiogenesis profiles based on the tissue analysis that would predict for success of receptor tyrosine kinase inhibitors and indicate appropriate situations for other therapies.
Bladder cancer
Abstract 4522 — This is a study of patients with muscle-invasive bladder cancer who were candidates for radical cystectomy and received neoadjuvant cisplatin-based chemotherapy. Patients for whom neoadjuvant cisplatin-based chemotherapy resulted in clinical complete response — negative ‘radical’ TURBT, urine cytology and CT imaging — who opted for surveillance and no further surgery were followed. The researchers asked the question: Is it possible for chemotherapy alone to control muscle-invasive bladder cancer? The answer was, “perhaps.”
Of the 148 patients with clinical complete response following neoadjuvant cisplatin-based chemotherapy were assessed. Among these patients, 48% had a first indication of recurrent cancer in the bladder. Of these, 16 patients had muscle-invasive disease and 55 had superficial disease; the latter were managed without cystectomy. In the overall cohort, the 5-year cystectomy-free survival rate was 76% and the 5-year RFS rate was 64%. Disease-specific survival was 90%. The bottom line here is that it is possible to treat patients with muscle-invasive bladder cancer with neoadjuvant cisplatin-based chemotherapy alone. This raises the question of whether an even better systemic therapy could further increase the success of systemic therapy and avoid cystectomy.
Abstract 4507 — For this pilot study, researchers administered the checkpoint inhibitor pembrolizumab (Keytruda, Merck) as neoadjuvant therapy prior to cystectomy. Results showed that pembrolizumab was able to eliminate detectable tumor in 32% of patients treated. This indicates that pembrolizumab, and presumably other checkpoint inhibitors that have shown activity in bladder cancer, can be safely given prior to cystectomy. Moreover, the therapy does not disrupt the ability to perform cystectomy and the cancer can be obliterated at rates similar to those achieved with standard neoadjuvant chemotherapy. This suggests that studies should explore appropriate combinations of cytotoxic therapy and immune-modulating agents to maximize local and systemic control in patients with muscle-invading bladder cancer and potentially define an approach to avoid cystectomy altogether. – by Jennifer Southall