Benjamin P. Saylor

In hormone-sensitive prostate cancer, an alternative dosing of docetaxel plus Nubeqa and ADT was associated with improvements in side effect rates.

Among patients with hormone-sensitive prostate cancer, an alternative dosing regimen of docetaxel — 50 mg/m

once every three weeks — plus Nubeqa (darolutamide) and androgen deprivation therapy (ADT) was associated with statistically significant and clinically meaningful improvements in severe, life-threatening and fatal side effect rates as well neutropenia and death of any reason, study results have shown.

The findings, from the phase 3 ARASAFE study, were presented at the 2025 European Society for Medical Oncology Congress in Berlin by Dr. Marc-Oliver Grimm, professor and chair of urology at Jena University Hospital in Jena, Germany.

By way of background, Grimm explained that the use of ADT, Nubeqa and docetaxel is FDA approved for patients with mHSPC based on findings from the phase 3 ARASENS trial. In that regimen, the docetaxel dosage is 75 mg/m

once every three weeks. However, Grimm pointed out that toxicity such as neutropenic complications could limit the use of this regimen compared with androgen receptor pathway inhibitor/ADT doublet therapy. For ARASAFE, Grimm and his co-authors sought to evaluate toxicity in triplet therapy with Nubeqa/ADT/docetaxel with docetaxel dosages of 50 mg/m

Neutropenia: a condition where the number of neutrophils (a type of white blood cell that helps fight infections) is lower than normal. This can make it easier to get infections.

Overall Survival: the length of time from the start of treatment that patients are still alive. It’s a way doctors measure how well a treatment works.

Leukopenia: a condition where there are fewer white blood cells than normal. White blood cells help protect the body from infections.

Prostate-Specific Antigen (PSA): a protein made by the prostate gland. PSA levels are often checked with a blood test to help detect or monitor prostate cancer.

“We hypothesized that triplet therapy with [Nubeqa], ADT and 50 mg[/m

] every two weeks reduces grade 3 (severe) to 5 (fatal) adverse events compared to the standard 75-mg[/m

] schedule,” Grimm said. Grimm also pointed to previous research indicating that ADT plus docetaxel 50 mg/m

once every two weeks was associated with better time to treatment failure and fewer grade 3 to 4 (life-threatening) side effects in patients with metastatic castration-resistant prostate cancer.

In ARASAFE, a total of 250 patients with mHSPC were randomly assigned to Nubeqa 600 mg twice daily plus ADT plus six cycles of docetaxel 75 mg/m

once every three weeks (three-week cycle, 129 patients) or to Nubeqa 600 mg twice daily plus ADT plus six cycles of docetaxel 50 mg/m

once every two weeks (four-week cycle, 121 patients). Total expected docetaxel dose was 450 mg/m

Primary end points included grade 3 to 5 side effects and grade 3 to 4 neutropenia or death of any reason. Secondary end points included time to castration-resistant prostate cancer, overall survival, time to pain progression, time to first symptomatic skeletal event, time to initiation of subsequent systemic antineoplastic therapy, time to worsening of disease-related physical symptoms and quality of life.

Median age at baseline was 68 years in the 75 mg/m

arm. High-volume disease was present in 108 (83.7%) patients in the 75 mg/m

arm versus 104 (86%) patients in the 50 mg/m

arm. Mean number of docetaxel doses was 5.6 in the 75 mg/m

 arm. Mean cumulative docetaxel dose was 842.8 mg in the 75 mg/m

Grimm reported that the study reached its primary end points: The grade 3 to 5 side effect rate was 78.9% in the 75 mg/m

 arm. Additionally, the grade 3 to 4 neutropenia/death of any reason rate was 64.1% in the 75 mg/m

Grimm also reported that the rates of neutropenia, leukopenia and febrile neutropenia favored the 50 mg/m

The investigators utilized prostate-specific antigen (PSA) response at week 26 as a putative surrogate for oncologic outcome. Grimm reported that the median PSA level in the 75 mg/m

 arm was 0.16 ng/mL versus 0.26 ng/mL in the 50 mg/m

 arm. PSA levels of 0.2 ng/mL or lower were observed in 63 (48.8%) patients in the 75 mg/m

 arm versus 50 (41.3%) patients in the 50 mg/m

“In summary, ARASAFE demonstrates a statistically highly significant and clinically meaningful reduction in the incidence of grade 3 to 5 [side effect] rate and the rate of grade 3 to 4 neutropenia or death regardless of reason for the experimental approach. This was achieved despite higher total doses of docetaxel in the experimental arm. Therefore, the ARASAFE approach may be considered a potential new standard of care,” Grimm said in his concluding remarks.

“3-weekly docetaxel 75 mg/m2 vs 2-weekly docetaxel 50 mg/m2 in combination with darolutamide + ADT in patients with mHSPC: Results from the randomised phase III ARASAFE trial,” by Dr. Marc-Oliver Grimm, et al. Presented at: European Society for Medical Oncology Congress. October 17-21, 2025. Berlin, Germany. LBA92.

“FDA approves darolutamide tablets for metastatic hormone-sensitive prostate cancer,” FDA; https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-darolutamide-tablets-metastatic-hormone-sensitive-prostate-cancer

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Articles

An alternative dosing regimen of docetaxel, combined with darolutamide and androgen deprivation therapy, significantly reduced severe side effects and neutropenia in hormone-sensitive prostate cancer patients. The ARASAFE study compared a 50 mg/m2 biweekly docetaxel dose to the standard 75 mg/m2 triweekly dose, showing a lower incidence of grade 3 to 5 side effects and neutropenia in the experimental group. Despite a higher cumulative docetaxel dose, the experimental regimen demonstrated improved safety profiles, suggesting it as a potential new standard of care.

Alternative Docetaxel Dosing Reduces Toxicity Risk in Prostate Cancer

Among patients with muscle-invasive bladder cancer, perioperative Imfinzi to chemotherapy doesn’t have a detrimental effect on patient-reported outcomes.

Among patients with muscle-invasive bladder cancer, the addition of perioperative Imfinzi (durvalumab), meaning it is administered before and after surgery, to neoadjuvant, or presurgical chemotherapy, has been found to not have a detrimental effect on patient-reported outcomes, according to newly reported health-related quality of life data from the phase 3 NIAGARA trial.

Dr. Michiel van der Heijden, medical oncologist at the Netherlands Cancer Institute in Amsterdam, presented the findings at the 2025 European Society for Medical Oncology Congress in Berlin, Germany.

At last year’s ESMO Congress in Barcelona, Spain, Dr. Thomas B. Powles presented findings from NIAGARA. The patient population consisted of adults with cisplatin-eligible muscle-invasive bladder cancer, urothelial cancer or urothelial cancer with divergent differentiation or histologic subtypes, evaluated and confirmed for radical cystectomy, and with creatine clearance of 40 mL/min or lower. Patient were randomly assigned to either the Imfinzi arm or the comparator arm. Patients in the Imfinzi arm received neoadjuvant Imfinzi, 1500 mg intravenously every three weeks and gemcitabine plus cisplatin for four cycles followed by radical cystectomy and eight cycles of adjuvant, or postsurgical, Imfinzi. Patients in the comparator arm received four cycles of gemcitabine plus cisplatin followed by radical cystectomy. Median follow-up was 42.3 months.

Data from NIAGARA supported the U.S. Food and Drug Administration (FDA)’s approval of neoadjuvant Imfinzi in combination with gemcitabine and cisplatin, followed by adjuvant durvalumab monotherapy following radical cystectomy, or surgical removal of the bladder, for adult patients with muscle invasive bladder cancer.

At ESMO 2025, van der Heijden presented health-related quality of life outcomes from the NIAGARA study. In NIAGARA, the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and EQ-5D-5L were assessed via electronic device at baseline and every four weeks until disease progression. van der Heijden explained that the EORTC QLQ-C30 measures global health scale (GHS)/QoL as well as functional and symptom subscales. GHS/QoL and Physical, Fatigue, and Pain were included in NIAGARA as prespecified priority subscales, with a 10-point change in score compared with baseline being deemed clinically meaningful.

The EQ-5D-5L visual analogue scale is constructed for patients to rate their current overall health; for NIAGARA, the investigators reported visual analogue scale change from baseline.

A total of 439 (82.4%) of patients in the durvalumab arm completed the baseline EORTC QLQ-C30 assessment versus 450 (84.9%) patients in the comparator arm. In addition, 416 (78.0%) patients in the Imfinzi arm completed the baseline and at least one postbaseline assessment versus 410 (77.4%) of patients in the comparator arm. The compliance rate range from baseline to adjuvant week 29 was 50.9% to 82.4% in the durvalumab arm versus 44.3% to 84.9% in the comparator arm.

For the EQ-5D-5L, 417 (78.2%) patients completed the baseline assessment versus 430 (81.1%) patients in the comparator arm. Further, 391 (73.4%) patients in the Imfinzi arm completed the baseline and at least one postbaseline assessment versus 380 (71.7%) patients in the comparator arm. The compliance rate range from baseline to adjuvant week 29 was 49.9% to 78.2% in the Imfinzi arm versus 43.2% to 81.1% in the comparator arm.

For GHS/QoL, van der Heijden reported that that the difference between arms for overall mean change from baseline (CFB) was 1.6, and with the Physical Functioning subscale, the difference between arms for overall CFB was 1.2. For the Fatigue subscale, the difference between arms for overall CFB was –0.9, and for the Pain subscale, the difference between arms for overall CFB was –2.1.

The EQ-5D-5L visual analogue scale “also did not show any difference between the treatment arms,” according to van der Heijden.

“Overall, the addition of perioperative Imfinzi to neoadjuvant chemotherapy significantly improved event-free survival and overall survival without adversely affecting patient-reported outcomes,” van der Heijden said in his concluding remarks.

van der Heijden M, Powles TB, Galsky MD, et al. Health-related quality of life (HRQOL) outcomes from the NIAGARA trial of perioperative durvalumab (D) plus neoadjuvant chemotherapy (NAC) in muscle-invasive bladder cancer (MIBC). Presented at: European Society for Medical Oncology Congress. October 17-21, 2025. Berlin, Germany. Abstract 3069MO. https://s3.eu-central-1.amazonaws.com/m-anage.com.storage.esmo/static/esmo2025_abstracts/3069MO.html.pdf

Powles TB, van der Heijden MS, Galsky MD, et al. A randomized phase III trial of neoadjuvant durvalumab plus chemotherapy followed by radical cystectomy and adjuvant durvalumab in muscle-invasive bladder cancer (NIAGARA). Presented at: 2024 European Society for Medical Oncology Annual Congress. September 13-17, 2024. Barcelona, Spain. Abstract LBA5. https://cslide.ctimeetingtech.com/esmo2024/attendee/confcal/session/calendar?q=LBA5

Powles T, Catto JWF, Galsky MD, et al. Perioperative durvalumab with neoadjuvant chemotherapy in operable bladder cancer. 

. Published online September 15, 2024. Accessed October 17, 2025. https://www.nejm.org/doi/abs/10.1056/NEJMoa2408154

FDA approves durvalumab for muscle invasive bladder cancer. News release. US Food & Drug Administration. Published online March 28, 2025. Accessed October 17, 2025. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-durvalumab-muscle-invasive-bladder-cancer

IMFINZI (durvalumab) approved in the US as first and only perioperative immunotherapy for patients with muscle-invasive bladder cancer. News release. AstraZeneca. Published online March 31, 2025. Accessed October 17, 2025. https://www.astrazeneca-us.com/media/press-releases/2025/IMFINZI-durvalumab-approved-in-the-US-as-first-and-only-perioperative-immunotherapy-for-patients-with-muscle-invasive-bladder-cancer.html

The addition of perioperative durvalumab (Imfinzi) to neoadjuvant chemotherapy in muscle-invasive bladder cancer patients does not negatively impact patient-reported outcomes, as shown by the NIAGARA trial. The trial involved patients receiving neoadjuvant Imfinzi with chemotherapy, followed by radical cystectomy and adjuvant Imfinzi. Health-related quality of life was assessed using EORTC QLQ-C30 and EQ-5D-5L scales, showing no significant differences between treatment arms. The study supports FDA approval of this regimen, highlighting improved event-free and overall survival without compromising quality of life.

Imfinzi Not Associated With Bladder Cancer Quality of Life Decline

Keytruda (pembrolizumab) plus platinum-based chemotherapy was both safe and efficacious in treating penile squamous cell carcinoma (PSCC), according to findings from the phase 2 HERCULES trial presented at the 2024 

American Society of Clinical Oncology Annual Meeting

A phase 2 trial called HERCULES investigated the use of Keytruda (pembrolizumab) combined with platinum-based chemotherapy as a first-line treatment for advanced penile squamous cell carcinoma (PSCC).

The study found that the treatment was safe and efficacious.

A total of 39.4% patients responded to the treatment, with one complete response (disappearance of cancer) and 12 partial responses.

Penile squamous cell carcinoma is a rare disease with a poor prognosis, and platinum-based chemotherapy has been the standard treatment.

Dr. Fernando Cotait Maluf, of Hospital Beneficência Portuguesa de São Paulo and Hospital Israelita Albert Einstein, São Paulo, Brazil, presented the data at the conference. In the presentation, Maluf noted that PSCC has up to a 10 times higher incidence in low-income countries in Africa, Asia and Latin America.He added that advanced PSCC is a disease for which no improvements have been made of late, and prognosis is poor, with an overall survival (OS; time patients live before death of any cause) of approximately six to seven months.

“Platinum-based chemotherapy has been considered the standard of care. … Immune checkpoint inhibitors have been associated with efficacy in different tumor types, including HPV16-positive tumors, such as cervical and head and neck squamous cell carcinoma,”Maluf explained.

Maluf and his coauthors hypothesized that the addition of Keytruda to platinum-based chemotherapy for first-line treatment of advanced penile cancer would be safe and associated with improved outcomes for patients.

Eligible patients were required to have an ECOG performance status of 0 to 1 (meaning that they were able to perform all their daily tasks independently), have metastatic disease, locally advanced disease that is not eligble to curative-intent therapy, loco-regional recurrence (cancer that returned to or nearby the original site) that is not amenable to curative-intent therapy, and no prior exposure to chemotherapy for advanced disease. However, prior presurgical chemotherapy was allowed if disease progressed after 12 months.

A total of 37 patients were included in the study, of whom five (13.5%) had locally advanced disease and eight (21.6%) had loco-regional recurrence. Thirty-three patients were eligible for an analysis to determine how well the treatment regimen worked.

The main goal of the trial was confirmed overall response rate (ORR; percentage of patients whose disease shrinks or disappears), as determined by the investigators on the study. Secondary goals included confirmed ORR by experts not involved in the trial, progression-free survival (PFS; time patients live without disease worsening), OS, safety and analysis of how this research may be able to influence cancer care for this population.

Confirmed ORR by researchers was 39.4%. Of these, one was a complete response, meaning that all signs of cancer disappeared (3%), and 12 (36.4%) were partial responses, meaning that the cancer shrunk but was still detectable on follow-up tests.

Confirmed ORR by experts unaffiliated with the study was 42.4%. Clinical benefit rate (percentage of patients who experience a complete response, partial response or stable disease) by researchers more than 24 weeks was 45.5%.

Maluf reported that tumor shrinkage of any magnitude was seen in 75.8% of patients. After a median follow-up of 24 months, median duration of response was 5.9 months and median time to response was 1.4 months. Median PFS was 5.4 months, and median OS was 9.6 months.

“Our biomarker exploratory analysis showed a potential correlation between response with [tumor mutational burden] as well as HPV16 status,” Maluf reported.

Regarding treatment-related side effects, Maluf reported 19 side effects (51.4%) of grade 3 (moderate) or higher and noted that only six patients (16.2%) experienced neutropenia (decrease in a type of white blood cells). Two (5.4%) immune-related side effects of grade 3 or higher were observed.

“The HERCULES trial is the first trial to demonstrate the efficacy of immune checkpoint inhibitors in [patients with] advanced penile cancer with [a] manageable safety profile. We are proud to say that [Keytruda] plus platinum-based therapy is a new treatment option for [patients with] advanced penile cancer,” Maluf said in his concluding remarks.

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Keytruda plus platinum-based chemotherapy appeared to be safe and effective in treating penile squamous cell carcinoma. 

Keytruda Plus Chemo May Improve Penile Cancer Outcomes

The treatment combination of Welireg (belzutifan) and Cabometyx (cabozantinib) demonstrated durable anti-tumor activity in patients with clear cell renal cell carcinoma (ccRCC) who were treatment-naïve or had previous treatment with immunotherapy, according to results from a phase 2 trial.

The data from the phase 2 trial, LITESPARK-003, were presented at the 

2023 European Society for Medical Oncology (ESMO) Annual Congress

 in Madrid, Spain by Dr. Toni K. Choueiri, professor of medicine at Harvard Medical School and an attending physician, director of the Genitourinary Oncology Disease Center, and director of the Lank Center for Genitourinary Oncology at the Dana-Farber Cancer Institute in Boston, Massachusetts.

In his presentation, Choueiri explained that the inactivation of the von Hippel-Lindau gene (VHL; a mutated gene that increases the growth of abnormal cells) results in the overexpression of hypoxia-inducible factors (HIFs; proteins responsible for cell responses to changes in oxygen levels and activate specific genes for cell growth and survival).

Choueiri added that initial results from LITESPARK-003 showed promising anti-tumor activity in patients who were either treatment naïve (cohort 1) or previously treated with immunotherapy (cohort 2).

Cohort 1 had 50 patients enrolled and treated, with a median follow-up of 24.3 months; however, 24 patients discontinued treatment. Cohort 2 had 52 patients enrolled and treated, with a median follow-up of 39.8 months. Forty-six patients discontinued treatment.

At a median follow-up of 14 months, there was a 57% overall response rate (ORR; percentage of patients who had a partial or complete response to treatment) in cohort 1. At a median follow-up of 24.6 months, there was a 31% ORR in cohort 2. At the 2023 ESMO Congress, Choueiri presented updated findings from both cohorts.

In cohort 1, 28 patients (56%) were International Metastatic RCC Database Consortium (IMDC) favorable risk, and 22 patients (44%) were IMDC intermediate/poor risk. In cohort 2, 11 patients (21%) were IMDC favorable risk and 41 patients (79%) were IMDC intermediate/poor risk.

Choueiri reported that ORR in cohort 1 was 70% in the entire cohort, 79% in patients who were International Metastatic Renal Cell Carcinoma Database Consortium (IMDC) favorable risk and 59% in patients who were IMDC intermediate/poor risk.

In cohort 2, ORR was 31% in the entire cohort, and 27% in patients who were IMDC favorable risk and 32% in patients who were IMDC intermediate/poor risk.

Choueiri reported that all patients in cohort 1 had a reduction in target lesion size and that in cohort 2, 45 of 51 patients (88%) with available post-baseline imaging saw a reduction in target lesion size.

In cohort 1, the median progression-free survival (PFS; time during and after treatment when the patient lives and the cancer does not worsen) was 30.3 months, and in cohort 2, the median PFS was 13.8 months. In cohort 1, the median overall survival (OS; length of time from diagnosis or start of treatment when a patient still lives) was not reached (meaning more than half of the patients in that cohort had not died) and in cohort 2, the median PFS was 26.7 months.

Any-grade treatment-related side effects were reported in 100% of cohort 1 and 98% of cohort 2. Treatment-related side effects of grade 3 or higher (mild to severe) occurred in 23 patients (46%) in cohort 1 and 33 patients (64%) in cohort 2.

There were no treatment-related deaths in cohort 1, but one patient experienced treatment-related death in cohort 2. Seven patients (14%) in cohort 1 discontinued any drug because of treatment-related side effects, and 11 patients (21%) in cohort 2 discontinued any drug because of treatment-related side effects.

Serious treatment-related side effects were observed in seven patients (14%) in cohort 1 and 16 patients (31%) in cohort 2, with dose reduction because a treatment-related side effect occurred in 38 patients (76%) and 37 patients (71%) in cohorts 1 and 2, respectively.

“(Welireg) plus (Cabometyx) continue to show durable anti-tumor activity in patients with clear cell RCC who are treatment-naïve or previously treated,” Choueiri concluded.

The Welireg-Cabometyx treatment combination demonstrated anti-tumor activity for some patients with clear cell renal carcinoma, according to a phase 2 trial.


Benjamin P. Saylor

Alternative Docetaxel Dosing Reduces Toxicity Risk in Prostate Cancer

Imfinzi Not Associated With Bladder Cancer Quality of Life Decline

Keytruda Plus Chemo May Improve Penile Cancer Outcomes

Welireg Plus Cabometyx Shows Anti-Tumor Activity in Kidney Cancer Type

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