Advertisement


Neeraj Agarwal, MD, on Prostate Cancer: New Data on Talazoparib and Enzalutamide

2023 ASCO Genitourinary Cancers Symposium

Advertisement

Neeraj Agarwal, MD, of the Huntsman Cancer Institute, University of Utah, discusses phase III results from the TALAPRO-2 study, which suggested an improvement in radiographic progression-free survival with the combination of talazoparib and enzalutamide over standard-of-care enzalutamide alone as first-line treatment in patients with metastatic castration-resistant prostate cancer. The improvement was seen regardless of homologous recombination repair gene mutations. The combination regimen delayed the time to chemotherapy and worsening in global health status and quality of life. (Abstract LBA17).



Transcript

Disclaimer: This video transcript has not been proofread or edited and may contain errors.
TALAPRO-2 trial is a randomized controlled trial. It is a phase III trial which recruited patients who are in first-line metastatic CRPC setting. So, essentially, these patients had newly diagnosed metastatic castrate-resistant prostate cancer. These patients were randomized to the combination of enzalutamide plus talazoparib versus enzalutamide plus placebo. This was a placebo controlled trial for talazoparib, and enzalutamide was received by all patients. It is important to note that the trial had two components, two cohorts, cohort one and cohort two. Cohort one is the one which was recruited first, included all-comer population regardless of presence of homologous recombination repaired gene alterations, and cohort two is a second portion of the trial, which is still ongoing. Cohort two was recruited after cohort one finished recruitment, and cohort two has patients to have homologous recombination repair gene alterations. In the ASCO GU 2023, we reported the result only of those cohort one patients. These are 805 patients who were randomized to this enzalutamide plus talazoparib versus enzalutamide plus placebo arm. Radiographic progression-free survival was the primary endpoint and it had to be assessed by independent radiology review, so independent central review assessment was done for these scans. All the patients were tested, prospectively, by tumor tissue testing for the absence or presence of homolog three combination repair gene alterations, and this was a stratification factor in this trial. Other stratification factor was the receipt of abiraterone or docetaxel chemotherapy in the castration-sensitive setting. As I said, patients could not have received any of these medicines for castration-resistant state, but they could have received these drugs for castration-sensitive setting. Let's talk about the results of the TALAPRO-2 trial. We saw the primary endpoint was met, radiographic progression-free survival was significantly longer with talazoparib plus enzalutamide versus enzalutamide plus placebo. There was a 37% reduction in risk of death, with the hazard ratio of 0.63 favoring the enzalutamide and talazoparib arm. Importantly, when we looked at the pre-specified stratification factors of HRR negative patients, HHR positive patients, or HRR negative plus unknown groups, in both groups, the improvement in survival was significant. So, if you look at patients who are HRR gene alteration positive, there was a 54% reduction in risk of progression or death with talazoparib in patients who belong to HRR unknown or HRR negative status, there was a 30% reduction in risk of death or progression. Now, if you look at those patients, and this was an exploratory analysis which was done to make sure that we are not seeing any false signal in the HRR negative or HRR unknown cohort, we specifically looked at those patients who were HRR negative by prospective tumor tissue testing. We found that even this group of patients who were HRR negative by tumor tissue testing, there was a significant improvement in radiographic progression-free survival with enzalutamide with talazoparib, and there was a 34% reduction in risk of progression or death. There was a significant delay of chemotherapy, significant delay of progression or death on first subsequent therapy, there was a significant delay of deterioration of quality of life and global health status. So all those clinically meaningful endpoints were met, which were meaningful to our patients. Overall survival data are immature and right now hazard ratio is 0.89 favoring talazoparib plus enzalutamide. Regarding the side effects, most of them were cytopenias. Anemia was commonly present, but I would like to highlight that 49% of these patients had grade 1 or 2 anemia before actually starting any treatment at baseline. So, we saw anemia in 46% patients, which is grade 3 or 4, but these all happened in first three months, and protocol did not actually require dose reduction of talazoparib until anemia was grade 3 and 4 because so many patients had grade 1 and 2 anemia at baseline. But after patients reached grade 3/4 anemia, protocol required them to reduce the dose of talazoparib. After that, talazoparib was well tolerated and there was only 8% patients who had to discontinue because of anemia. So, bottom line from this trial, we saw enzalutamide plus talazoparib significantly improving radiographic progression-free survival, along with meeting many other clinically relevant endpoints in this first-line mCRPC patient population, regardless of homologous recombination repair gene alterations.

Related Videos

Kidney Cancer

Thomas Powles, MD, PhD, on Renal Cell Carcinoma: Phase III Results on Cabozantinib, Nivolumab, and Ipilimumab

Thomas Powles, MD, PhD, of Barts Health NHS Trust, Queen Mary University of London, discusses new data from the COSMIC-313 study of patients with advanced renal cell carcinoma of IMDC (International Metastatic RCC Database Consortium) intermediate or poor risk. Those who received cabozantinib instead of placebo with nivolumab and ipilimumab as first-line treatment seemed to experience improved progression-free survival. A subgroup analysis suggested the benefit was primarily in patients with an intermediate risk. Follow-up for overall survival is ongoing. (Abstract 605).

Kidney Cancer

Laurence Albiges, MD, PhD, on Renal Cell Carcinoma: New Phase II Data on Cabozantinib and Checkpoint Inhibitor Therapy

Laurence Albiges, MD, PhD, of France’s Gustave Roussy Cancer Centre, discusses interim results from the CaboPoint study, which evaluated cabozantinib as second-line treatment in patients with unresectable, locally advanced or metastatic renal cell carcinoma with a clear cell component. Disease in the study participants had progressed after prior treatment with ipilimumab and nivolumab in combination or combined with VEGF-targeted therapy. (Abstract 606).

Bladder Cancer

Andrea Necchi, MD, on Bladder Cancer: Phase II Results With Pembrolizumab Monotherapy

Andrea Necchi, MD, of Italy’s Vita-Salute San Raffaele University and the IRCCS San Raffaele Hospital and Scientific Institute, discusses new data from the KEYNOTE-057 trial on a novel systemic therapy for papillary high-risk non–muscle-invasive bladder cancer. The findings suggest that patients whose disease does not respond to bacillus Calmette-Guérin or who declined or were ineligible for a radical cystectomy may benefit from pembrolizumab monotherapy. (Abstract LBA442).

Bladder Cancer

Aristotelis Bamias, MD, on Urothelial Carcinoma: Final Overall Survival Analysis of Atezolizumab Monotherapy vs Chemotherapy

Aristotelis Bamias, MD, of the National and Kapodistrian University of Athens, discusses results from the phase III IMvigor130 study, which suggest that atezolizumab monotherapy continues to show better tolerability vs chemotherapy for patients with untreated locally advanced or metastatic urothelial carcinoma. (Abstract LBA441).

Prostate Cancer

Daniel P. Petrylak, MD, on Prostate Cancer: Latest Data on Pembrolizumab Plus Docetaxel

Daniel P. Petrylak, MD, of the Yale Cancer Center, discusses phase III findings from the KEYNOTE-921 study, which was designed to assess the combination of pembrolizumab and docetaxel in the treatment of patients with metastatic castration-resistant prostate cancer. They had not received chemotherapy, but their disease progressed on the next-generation hormonal agent, or they could not tolerate the agent. (Abstract 19).

Advertisement

Advertisement




Advertisement