Event-free survival (EFS) and overall survival (OS) rates were high at 12- and 36-months among patients with muscle-invasive urothelial carcinoma treated with neoadjuvant avelumab (Bavencio) plus cisplatin-based chemotherapy, according to data from the phase 2 AURA trial (NCT03674424) presented at the 2024 

“In the cisplatin-eligible cohorts, we showed that high EFS and OS rates can be achieved at 12 and 36 months in patients treated with neoadjuvant avelumab in combination with cisplatin-based chemotherapy, and in particular, in patients treated with the dose-dense MVAC [ddMVAC] regimen. In the cisplatin-ineligible cohort, as expected, we show a lower survival outcome at 12 months with no additional benefit of [the] paclitaxel/gemcitabine regimen,” lead author Jeremy Blanc, MD, of the Institut Jules Bordet, Hôpital Universitaire de Bruxelles, and Université Libre de Bruxelles, said during the presentation.

In the cisplatin-eligible cohort, the 12- and 36-month EFS rate among those receiving the ddMVAC regimen was 92% and 79%, respectively. The 12- and 36-month EFS rate among those receiving gemcitabine/cisplatin plus avelumab was 84% and 62%, respectively. Regarding OS, those receiving the ddMVAC regimen achieved an OS rate of 95% at 12 months and 85% at 36 months. Those receiving gemcitabine/cisplatin plus avelumab achieved an OS rate of 92% at 12 months and 64% at 36 months.

In the cisplatin-ineligible cohort, the 12-month EFS rate was 64% among patients who received avelumab alone and 60% among those who received paclitaxel/gemcitabine plus avelumab. The 12-month OS rate was 79% among those who received avelumab alone and 82% among those who received paclitaxel/gemcitabine plus avelumab. At the time of data report, 36-month data for these patients were not yet mature.

Data from both the cisplatin-eligible cohorts and the cisplatin-ineligible cohorts also showed that achieving a pathological complete response was associated with improved OS.

“As we know, cisplatin-based neoadjuvant chemotherapy followed by surgery is the standard treatment in non-metastatic muscle invasive bladder cancer. Unfortunately, nearly half of the patients are not fit enough to receive cisplatin-based chemotherapy,” Blanc said.

In AURA patients were stratified by cisplatin eligibility. Patients who were eligible for cisplatin were randomly assigned 1:1 to either gemcitabine/cisplatin plus avelumab or to ddMVAC plus avelumab. Patients who were not eligible to receive cisplatin were randomly assigned 1:1 to receive paclitaxel/gemcitabine plus avelumab or to avelumab alone.

Previously reported data from the study showed a pathological complete response rate of 58% with ddMVAC, 52% with gemcitabine/cisplatin plus avelumab, 32% with avelumab alone, and 14% with paclitaxel/gemcitabine plus avelumab. The current analysis focused on the key secondary end points of EFS and OS.

The phase 2 AURA trial is a multi-centric, randomized, non-comparative study to explore neoadjuvant avelumab alone or in combination with chemotherapy. To be included in the trial, patients needed to have pathologically-confirmed MIUC with planned radical cystectomy and lymphadenectomy.

The primary end point for the trial was the proportion of patients who achieved a pathological complete response. Secondary end points included the proportion of patients who achieved a <ypT2N0, safety, and EFS and OS at the 12- and 36-month time points.

“We know that further investigation through a phase 3 trial is very important to validate our findings. We believe that the identification of biomarkers could also optimize muscle-invasive bladder cancer care and patient selection,” Blanc concluded in the presentation.

Blanc J, Carnot A, Barthelemy P, et al. Avelumab (A) as neoadjuvant therapy in patients (pts) with muscle-invasive urothelial carcinoma (MIUC): Survival data of AURA trial, Oncodistinct 004. Presented at: 2024 American Society for Clinical Oncology Annual Meeting. May 31-June 4, Chicago, Illinois. Abstract 4516. https://ascopubs.org/doi/10.1200/JCO.2024.42.16_suppl.4516

Articles

High event-free survival (EFS) and overall survival (OS) rates were observed at 12 and 36 months in patients with muscle-invasive urothelial carcinoma treated with neoadjuvant avelumab plus cisplatin-based chemotherapy in the phase 2 AURA trial. Cisplatin-eligible patients showed better outcomes, particularly with the dose-dense MVAC regimen. Cisplatin-ineligible patients had lower survival outcomes. Achieving a pathological complete response correlated with improved OS. Further phase 3 trials and biomarker identification are necessary to optimize treatment and patient selection.

The addition of avelumab to cisplatin-based chemotherapy led to high event-free survival and overall survival rates in patients with muscle-invasive urothelial carcinoma.

Avelumab Plus Cisplatin-Based Chemotherapy Yields High EFS and OS Rates in MIUC

According to patient-reported outcome (PRO) data from the phase 3 EV-302 trial (NCT04223856), the frontline combination of enfortumab vedotin-ejfv (Padcev) and pembrolizumab (Keytruda; EV+P) did not negatively affect quality of life (QOL), pain, or functioning in patients with locally advanced or metastatic urothelial cancer.

Previously reported data from the EV-302 trial showed that the combination of EV+P nearly doubled PFS and OS vs chemotherapy in patients with locally advanced or metastatic urothelial cancer.

 Specifically, the median PFS was 12.5 months with EV+P, vs 6.3 months in the chemotherapy arm (HR, 0.45; 95% CI, 0.38-0.54; 

 < .001), and the median OS was 31.5 months in the EV+P arm compared with 16.1 months in the chemotherapy arm (HR, 0.47; 95% CI, 0.38-0.58; 

Updated data from the EV-302 trial were presented at the 2024 American Society for Clinical Oncology Annual Meeting in Chicago, Illinois by Shilpa Gupta, MD, director of Genitourinary Medical Oncology at Taussig Cancer Institute and Co-Leader of the Genitourinary Oncology Program at Cleveland Clinic in Cleveland, Ohio.

“We know that patients with locally advanced and metastatic urothelial cancer have a poor prognosis, with an estimated 5-year survival of less than 8% globally, and they have a high symptom and pain burden which impacts their quality of life and functioning,” Gupta noted during the presentation. “Here, we report the PRO data from the EV-302 trial, including impacts on patient's quality of life, functioning, and disease symptoms.”

Overall, at baseline, QOL and pain scores were balanced between the 2 arms.

Time to pain progression (TTPP) was previously reported, showing a median TTPP of 14.2 (6.6-not reached) months in the EV+P arm and 10.0 (5.9-not reached) months in the chemotherapy arm. No statistically significant difference between the 2 arms was observed (HR, 0.92; 95% CI, 0.72-1.2; 

Further, patients in the EV+P arm demonstrated larger improvements in worst pain per the Brief Pain Inventory Short Form (BPI-SF) assessment compared with those in the chemotherapy arm. However, neither arm reached the pre-defined thresholds for a clinically meaningful improvement.

Among those with moderate/severe pain at baseline (nearly one-third of patients), a clinically meaningful improvement in worst pain per BPI-SF was observed in both treatment arms. Those in the EV+P arm experienced greater improvements in pain compared with those in the chemotherapy arm.

The investigators also assessed changes in the EORTC Quality of Life Questionnaire (EORTC QLQ-C30), which measures global health status (GHS) and QOL. Patients in the EV+P arm demonstrated a transient worsening in GHS/QoL score at week 3, with a return to baseline at week 4. Patients in the chemotherapy arm demonstrated a worsening in GHS/QOL from week 1 through week 17, with a return to baseline from week 20. Overall, the median time to confirmed deterioration was 5.9 months in the EV+P arm vs 3.2 months in the chemotherapy arm (HR, 0.98; 95% CI, 0.79-1.2).

Among those with moderate/severe pain at baseline, patients in the EV+P arm showed a clinically meaningful improvement in GHS/QoL compared with the chemotherapy arm. Both cisplatin-eligible and cisplatin-ineligible patients in the EV+P arm showed a transient worsening in GHS/QOL through week 3, with a return to baseline at week 4. EV+P appeared to perform better in cisplatin-eligible patients compared with chemotherapy.

Additionally, patients in the EV+P arm demonstrated improved functioning across all functioning domains in the EORTC QLQ-C30 assessment compared with those in the chemotherapy arm, assessed by a change from baseline to week 26.

Overall, the patient compliance rate with the PRO assessments remained above 70% through week 17 in the chemotherapy arm and through week 29 in the EV+P arm. The investigators speculate that the difference may be due to differences in visit schedules after the end of protocol-defined treatment.

Safety data from the EV-302 study was consistent with previous studies and showed that EV+P was generally manageable.

In total, the EV-302 trial enrolled 886 patients with locally advanced or metastatic urothelial cancer who were randomly assigned 1:1 to receive either EV+P (n = 442) or to receive platinum-based chemotherapy (n = 444). All patients included in the trial were treated until disease progression, unacceptable toxicity, or the completion of maximum cycles. In the EV+P arm, there were no maximum cycles of EV, and there was a maximum of 35 cycles for pembrolizumab. In the chemotherapy arm, the maximum number of gemcitabine and platinum chemotherapy cycles was 6.

Patients filled out PRO questionnaires weekly for up to 12 weeks, equating to around 4 cycles, and then every 3 weeks after the end of treatment through disease progression and survival follow-up.

The primary end points for the trial were PFS per blinded independent central review (BICR) and OS. Key secondary end points included TTPP and change from baseline in BPI-SF worst pain at week 26.

Gupta concluded in the presentation, “The PRO data presented here complements the published clinical efficacy and safety data, add the patient's voice, and support the use of EV/pembro for patients with locally advanced/metastatic urothelial cancer.

1. Gupta S, Loriot T, Van der Heijden M, et al. Patient-reported outcomes (PROs) from a randomized, phase 3 trial of enfortumab vedotin plus pembrolizumab (EV+P) versus platinum-based chemotherapy (PBC) in previously untreated locally advanced or metastatic urothelial cancer (la/mUC). Presented at: 2024 American Society for Clinical Oncology Annual Meeting. May 31-June 4, Chicago, Illinois. Abstract 4502. https://ascopubs.org/doi/abs/10.1200/JCO.2024.42.16_suppl.4502

Powles T, Valderrama BP, Gupta S, et al. Enfortumab vedotin and pembrolizumab in untreated advanced urothelial cancer. 

. 2024;390(10):875-888. doi:10.1056/NEJMoa2312117

The combination of enfortumab vedotin-ejfv and pembrolizumab in the EV-302 trial did not negatively impact quality of life, pain, or functioning in patients with advanced urothelial cancer. The combination nearly doubled progression-free survival and overall survival compared to chemotherapy. Patients in the EV+P arm showed larger improvements in pain and functioning, although neither arm reached clinically meaningful thresholds. The trial enrolled 886 patients, and the primary endpoints were progression-free survival and overall survival, with secondary endpoints including time to pain progression and changes in pain scores.

Enfortumab vedotin plus pembrolizumab did not negatively affect quality of life in patients with advanced urothelial carcinoma.

PRO Data Add to Efficacy and Safety of Frontline Enfortumab Vedotin/Pembrolizumab in Advanced Urothelial Carcinoma

The addition of niraparib (Zejula) to abiraterone acetate (Zytiga) and prednisone (AAP) led to a benefit in overall survival (OS) vs treatment with AAP alone in patients with 

+) metastatic castration-resistant prostate cancer (mCRPC), according to data from the phase 3 MAGNITUDE trial (NCT03748641) presented at the 2023 ESMO Congress.

The OS analysis occurred at a median follow-up of 35.9 months (19.2 additional months from the primary analysis). The analysis focused on patients with 

+ status, which included 113 patients who received niraparib plus AAP and 112 patients who received placebo plus AAP.

Data showed a median OS of 30.4 months among patients who received niraparib plus AAP, compared with 28.6 months among those who received placebo plus AAP (HR, 0.788; 95% CI, 0.554-1.120; nominal 

 = .1828). A pre-planned multivariate analysis of pre-specified prognostic factors, including those numerically off-balance at baseline, corroborated the OS benefit in the experimental arm (HR, 0.663; 95% CI, 0.464-0.947; nominal 

Beyond OS, other secondary end points assessed in this final analysis included time to symptomatic progression (TSP), time to cytotoxic chemotherapy (TCC), and safety.

Treatment with niraparib plus AAP was associated with benefits in both TSP (HR, 0.562; 95% CI, 0.371-0.849; nominal 

 = .0056) and TCC (HR, 0.598; 95% CI, 0.387-0.924; nominal 

The median treatment duration was 20.5 months for those in the experimental arm and 14.4 months for those who received placebo plus AAP. Overall, 53.1% (60/113) of patients in the niraparib plus AAP arm discontinued treatment due to disease progression, compared with 76.8% (86/112) of patients in the placebo plus AAP arm.

There were no new safety signals that emerged from the longer follow-up. Adverse events were manageable in both arms, with differences driven by known hematologic toxicities associated with niraparib.

Previous findings from the primary analysis of the MAGNITUDE study showed an improvement in radiographic progression-free survival, the primary end point, with the combination of niraparib plus AAP compared with placebo/AAP in patients with 

 These data led to the FDA-approval of the regimen in this setting.

“The final analysis of MAGNITUDE supports the positive benefit-risk profile of first-line niraparib with abiraterone acetate plus prednisone, establishing niraparib with abiraterone acetate plus prednisone as a new standard of care for patients with 

+ mCRPC,” said presenting author Kim Nguyen N. Chi, MD, FRCPC, a professor in the department of medicine at the University of British Columbia in Vancouver, Canada.

1. Niraparib (NIRA) with abiraterone acetate plus prednisone (AAP) as first-line (1L) therapy in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) and homologous recombination repair (HRR) gene alterations: Three-year update and final analysis (FA) of MAGNITUDE. Presented at the European Society of Medical Oncology (ESMO) Congress. October 20-24, 2023. Madrid, Spain. Abstract LBA85

2.Chi KN, Sandhu S, Smith MR, et al. Niraparib plus abiraterone acetate with prednisone in patients with metastatic castration-resistant prostate cancer and homologous recombination repair gene alterations: second interim analysis of the randomized phase III MAGNITUDE trial. 

. Published online July 1, 2023. Accessed October 21, 2023. doi: 10.1016/j.annonc.2023.06.009

3. National Institutes of Health US National Library of Medicine ClinicalTrials.gov. A study of niraparib in combination with abiraterone acetate and prednisone versus abiraterone acetate and prednisone for treatment of participants with metastatic prostate cancer (MAGNITUDE). Last updated October 11, 2023. Accessed October 20, 2023. https://clinicaltrials.gov/study/NCT03748641

4. Phase 3 MAGNITUDE study: First results of niraparib (NIRA) with abiraterone acetate and prednisone (AAP) as first-line therapy in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC) with and without homologous recombination repair (HRR) gene alterations. Presented at the 2022 ASCO Genitourinary Cancers Symposium. February 17-19, 2022. San Francisco, California. Abstract 12

The addition of niraparib to abiraterone acetate and prednisone led to a benefit in overall survival vs treatment with AAP alone in patients with BRCA1/2-mutated metastatic castration-resistant prostate cancer.

Niraparib Plus Abiraterone and Prednisone Elicits OS Benefit in BRCA1/2+ mCRPC

Metastatic Castration-Resistant 
Prostate Cancer | Image Credit: 
© SciePro - stock.adobe.com

Treatment with the combination of lutetium Lu 177 vipivotide tetraxetan (Pluvicto; formerly 

Lu-PSMA-617) and enzalutamide (Xtandi) led to an improvement in prostate-specific antigen (PSA) progression-free survival (PSA-PFS) vs enzalutamide alone in patients with metastatic castration-resistant prostate cancer (mCRPC), according to interim findings from the phase 2 ENZA-p study (NCT04419402) presented at the 2023 ESMO Congress.

“This is the first randomized trial combining an androgen receptor signaling inhibitor, enzalutamide, with lutetium Lu 177 vipivotide tetraxetan. It provides strong evidence for an enhanced anti-cancer effect with the combination of enzalutamide and lutetium Lu 177 vipivotide tetraxetan based on the primary end point, PSA-PFS,” said Louise Emmett, MD, FRACP, during an oral presentation of the findings at the meeting. Emmett is the director of theranostics and nuclear medicine at St. Vincent’s Hospital in Sydney, Australia.

Data from the study showed a median PSA-PFS of 13 months with the combination therapy compared with 7.8 months with enzalutamide alone (HR, 0.43; 95% CI, 0.29-0.63; 

 = .00001). Median radiographic PFS was 16 months with the combination therapy compared with 12 months for enzalutamide alone (HR, 0.67; 95% CI, 0.44-1.01).

Further, PSA 50% (decrease ≥50% from baseline) response rates were 93% (77/83) in the combination arm, compared with 68% (54/79) for enzalutamide alone (

 < .001). PSA 90% (decrease ≥90% from baseline) response rates were 78% (65/83) among those in the combination arm compared with 37% (29/79) among those who received enzalutamide alone (

In total, the ENZA-p study included 162 patients with mCRPC. Patients were randomly assigned 1:1 to 160 mg of enzalutamide alone (n = 79) or 160 mg enzalutamide plus 7.5 GBq lutetium Lu 177 vipivotide tetraxetan (n = 83) delivered in 2 or 4 doses. Those included in the combination therapy arm underwent 2 doses with lutetium Lu 177 vipivotide tetraxetan with SPECT with 2 additional doses for those with persistent PSMA-positive disease detected at 92-day follow-up. In total, 81% of patients in the combination arm received 4 doses of lutetium Lu 177 vipivotide tetraxetan.

Emmett commented in the presentation, “We used 2 to 4 doses of Lu-PSMA in the ENZA-p trial, but 2 to 6 doses may further improve progression-free survival, particularly in those patients who have a high proportion of androgen persistent clones.”

The primary end point of the study was PSA-PFS. Secondary end points included radiological PFS, PSA50%, PSA90%, adverse effects (AEs), and overall survival (OS).

 Median follow-up among all patients included in the study was 20 months.

Serious AEs were reported in 35% (28/79) of patients who received enzalutamide alone, compared with 33% (27/81) of patients who received enzalutamide with lutetium Lu 177 vipivotide tetraxetan. Grade 4 or 5 AEs were reported among 4% (3/79) of patients in the enzalutamide monotherapy arm, compared with 6% (8/81) of patients in the combination arm.

In the presentation conclusion, Emmett noted, “I think this is going to become more important as we move this radiation treatment earlier in the disease paradigm to hormone sensitive prostate cancer. It [has] the potential to reduce toxicity by only administering if persistent PSMA-avid disease is present on the PSMA-PET or SPECT images.”

Emmett also added that there is planned follow-up of PFS and OS in the study until July 2024.

Enzalutamide and 177Lu-PSMA-617 in poor-risk, metastatic, castration-resistant prostate cancer (mCRPC): A randomised, phase II trial: ENZA-p (ANZUP 1901). Presented at the European Society of Medical Oncology (ESMO) Congress. October 20-24, 2023. Madrid, Spain. Abstract LBA84

National Institutes of Health US National Library of Medicine ClinicalTrials.gov. Enzalutamide with Lu PSMA-617 versus enzalutamide along in men with metastatic castration-resistant prostate cancer (ENZA-p). Last updated June 15, 2023. Accessed October 20, 2023. https://clinicaltrials.gov/study/NCT04419402

Treatment with the combination of lutetium Lu 177 vipivotide tetraxetan and enzalutamide led to an improvement in prostate-specific antigen progression-free survival vs enzalutamide alone in patients with metastatic castration-resistant prostate cancer.

Lutetium Lu 177 Vipivotide Tetraxetan Plus Enzalutamide Elicits PSA-PFS Improvement in mCRPC

Extended lymphadenectomy at the time of radical cystectomy did not produce a significant improvement in disease-free survival (DFS) or overall survival (OS) vs standard lymphadenectomy for patients with muscle-invasive bladder cancer (MIBC), according to data from the phase 3 SWOG S1011 trial (NCT01224665).

The findings were presented by lead author Seth P. Lerner, MD, FACS, at the 2023 ASCO Annual Meeting

“The primary objective of SWOG S1011 was to compare the disease-free survival in patients undergoing radical cystectomy, predominant urothelial, in extended node dissection plus standard vs standard alone. We define DFS as first documentation of relapse or recurrence or death due to any cause,” said Lerner during the presentation.Lerner is a professor of urology at Baylor College of Medicine in Houston, Texas.

In total, 618 patients were intraoperatively randomized to extended (n = 292) or standard (n = 300) lymphadenectomy across 27 sites in the United States and Canada. The median age of participants was 69.

Patients in the study had T2 to T4 disease, predominant urothelial, with the majority of patients presenting with T2 disease within both cohorts. Patients were recommended to receive adjuvant chemotherapy if they had locally advanced disease.

Lerner added, “If you had neoadjuvant chemotherapy, you needed to complete it 70 days prior to registration. And if you didn't, you had to undergo cystectomy within 4 weeks of registration.”

Median follow-up was 6.1 years for patients in both cohorts. Patients who underwent extended lymphadenectomy had a higher lymph node yield (41) compared with those who underwent standard lymphadenectomy (25). However, there was no significant difference in node metastasis between the arms, with a rate of 26% among patients receiving extended lymphadenectomy compared with 24% among patients receiving standard lymphadenectomy.

Overall, the data showed no significant difference in DFS for patients who underwent extended lymphadenectomy compared with patients who underwent standard lymphadenectomy (HR 1.10; 95% CI 0.87, 1.42, 

 = .40). OS among both cohorts was also found to be similar (HR 1.15 95% CI 0.89, 1.48, 

Grade 3/4 adverse events (AEs) were experienced by 16% of patients receiving extended lymphadenectomy compared with 8% receiving standard lymphadenectomy. Within 90 days of the procedure, 49% of patients who underwent extended lymphadenectomy experienced grade 3/4 AEs, compared with 42% of those who underwent standard. The most common AE in both arms was anemia, with the majority of cases being grade 3. Other AEs included urinary tract infection, sepsis, and ileus.

Patients who underwent extended lymphadenectomy had a 90-day mortality rate of 6.5% (19 patients), compared with 2.4% (7 patients) among those who underwent standard lymphadenectomy.

Lerner concluded, “The take-home message is that both the SWOG S1011 and the LEA trial [NCT01215071] show very clearly that a bilateral standard node dissection confined to the true pelvis is the standard of care for patients with curable muscle-invasive bladder cancer.”

Lerner SP, Tangen C, Svatek RS, et al. SWOG S1011: A phase III surgical trial to evaluate the benefit of a standard versus an extended lymphadenectomy performed at time of radical cystectomy for muscle invasive urothelial cancer. 

. 2023;41(suppl):4508. doi:10.1200/JCO.2023.41.16_suppl.4508

S1011: No extended node removal in bladder cancer. News release. SWOG Cancer Research Network. May 30, 2023. Accessed June 5, 2023. https://www.swog.org/news-events/news/2023/06/03/s1011-no-extended-node-removal-bladder-cancer

Extended lymphadenectomy at the time of radical cystectomy did not produce a significant improvement in disease-free survival (DFS) or overall survival (OS) vs standard lymphadenectomy for patients with muscle-invasive bladder cancer.

Extended Lymphadenectomy Does Not Lead to Survival Benefit in MIBC

The use of talazoparib (Talzenna) plus enzalutamide (Xtandi) was manageable with dose modifications or standard supportive care treatment in patients with metastatic castration-resistant prostate cancer (mCRPC), according to safety data from the phase 3 TALAPRO-2 study (NCT03395197) presented at the 2023 ASCO Annual Meeting.

“TALAPRO-2 is the first phase 3 study to evaluate talazoparib plus enzalutamide as a first-line treatment in patients with metastatic castration resistant prostate cancer, or mCRPC… Here we provide a detailed overview of the safety profile of talazoparib plus enzalutamide in the all-comers population of the TALAPRO-2 trial, with the aim of understanding how adverse events were managed,” said Arun Azad, MBBS, PhD, FRACP, during a presentation of the results. Azad is a medical oncologist at Peter MacCallum Cancer Centre in Australia.

Patients in the phase 3 TALAPRO-2 study were randomized 1:1 to receive 0.5 mg of talazoparib or placebo plus enzalutamide at 160 mg once daily. A total of 398 patients were included in the safety cohort of patients unselected for homologous recombination repair (HRR) gene alterations (all-comers).

At the point of study entry, 44.7% of patients had grade 1 anemia, and 4.3% had grade 2 anemia.

Data showed that 98.5% of patients experienced all-cause any-grade treatment emergent adverse events (TEAEs). Serious TEAEs were experienced in 19.6% of patients, and 19.1% discontinued treatment with talazoparib due to TEAEs. The rate of discontinuation of placebo due to TEAEs in the placebo/enzalutamide cohort was 12.2%.

The most common grade 3/4 TEAE in the talazoparib/enzalutamide arm was anemia (65.8%), which led to a discontinuation of treatment in 8.3% of patients. The median time to first onset of grade 3 or higher anemia in patients was 3.3 months, and the median duration was 16 days. Anemia was managed in patients using dose modification once anemia was grade 3 or higher, and/or with standard supportive care. Among all patients, 43.2% received dose reduction due to anemia.

“Despite dose reduction, the relative dose intensity of talazoparib remained high, above 80%. The incidence of talazoparib dose interruptions and reductions was similar during the all-comers and HRR deficient only populations. However, the rate of talazoparib discontinuation due to adverse events was about half in the HRR deficient cohort compared to the all-comers cohort,” said Azad.

Other common hematologic TEAEs in the all-comers cohort included neutropenia, which was observed in 35.7% of patients, and thrombocytopenia, which was observed in 24.6% of patients. Median onset of neutropenia was 2.3 months, and median duration was 12 days. Median onset of thrombocytopenia was 2.3 months, and median duration was 19 days.

The 3 most common non-hematologic TEAEs included fatigue (33.7%), back pain (22.1%), and decreased appetite (21.6%).

Overall, the median treatment duration of talazoparib was 19.8 months (range, 0.0-42.8). Grade 3 or higher TEAEs typically occurred early in treatment (within 6 months of starting treatment) and resolved in less than a month with dose modification and supportive care.

Similar incidence of all-cause TEAEs were seen between the all-comers cohort and the HRR deficient only cohort. 

TALAPRO-2 is an ongoing phase 3 study of talazoparib plus enzalutamide in patients with mCRPC. Patients were divided into 2 cohorts, made up of those with and without HRR gene alterations (all-comers) and an HRR-deficient only cohort.

The trial recently reported a clinically meaningful and statistically significant improvement in radiographic progression-free survival (rPFS) among patients receiving talazoparib plus enzalutamide versus placebo plus enzalutamide, regardless of HRR status.

At the time of data presentation, the median rPFS had not yet been met for patients receiving talazoparib and enzalutamide, compared with 21.9 months among those receiving placebo plus enzalutamide. Overall, the addition of talazoparib was found to reduce the risk of progression or death by 37% (HR, 0.63; 

Azad A, Fizazi K, Matsubara N, et al. Talazoparib (TALA) plus enzalutamide (ENZA) in metastatic castration-resistant prostate cancer (mCRPC): Safety analyses from the randomized, placebo (PBO)-controlled, phase 3 TALAPRO-2 study. 

Agarwal N, Azad A, Carles J, et al. TALAPRO-2: Phase 3 study of talazoparib (TALA) + enzalutamide (ENZA) versus placebo (PBO) + ENZA as first-line (1L) treatment in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC). 

The use of talazoparib plus enzalutamide was manageable with dose modifications or standard supportive care treatment in patients with metastatic castration-resistant prostate cancer.

Hannah Clarke