Hannah Clarke

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

Patients with locally advanced or metastatic urothelial cancer, a type of bladder cancer, experienced improvements in progression-free survival (PFS) and overall survival (OS) when 

treated with Padcev (enfortumab vedotin-ejfv) plus Keytruda (pembrolizumab)

 versus platinum-based chemotherapy without negative impact to quality of life (QOL), pain or functioning, according to patient-reported outcome (PRO) data from the phase 3 EV-302 trial.

In total, the EV-302 trial enrolled 886 patients with locally advanced or metastatic urothelial cancer who were assigned to receive either Padcev and Keytruda (442 patients) or to receive platinum-based chemotherapy (444 patients). All patients included in the trial were treated until disease progression, unacceptable toxicity or the completion of maximum cycles.

The combination of Padcev (enfortumab vedotin-ejfv) and Keytruda (pembrolizumab) for patients with locally advanced or metastatic urothelial cancer helped patients live longer overall (overall survival) and live longer without their disease worsening (progression-free survival), compared to chemotherapy.

The combination of Padcev and Keytruda did not negatively impact patients’ quality of life, pain levels or functioning.

Patients given Padcev and Keytruda lived for a longer period of time before their pain progressed compared to those given chemotherapy.

Previously reported data from the EV-302 trial

 showed that the combination of Padcev and Keytruda nearly doubled PFS (the time a patient lives without their disease spreading or progressing) and OS (the time a patient lives, regardless of disease status) when compared with chemotherapy in patients with locally advanced or metastatic urothelial cancer.

Specifically, the median PFS was 12.5 months with Padcev and Keytruda, versus 6.3 months in the chemotherapy group. The median OS was 31.5 months in the Padcev and Keytruda group, compared with 16.1 months in the chemotherapy group.

Updated data from the EV-302 trial were presented at 

the 2024 American Society for Clinical Oncology (ASCO) Annual Meeting

 by Dr. Shilpa Gupta, director of Genitourinary Medical Oncology at Taussig Cancer Institute and co-leader of the Genitourinary Oncology Program at Cleveland Clinic.

“We know that patients with locally advanced and metastatic urothelial cancer have a poor prognosis, with an estimated five-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.”

At the start of the trial, QOL and pain scores were similar among patients in the two treatment groups.

Time to pain progression (TTPP) was previously reported, showing a median TTPP of 14.2 months in the Padcev and Keytruda group and 10 months in the chemotherapy group. No statistically significant difference between the two groups was observed, meaning that researchers could not say with certainty that one treatment regimen truly led to a superior outcome.

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

Among those with moderate/severe pain at baseline (approximately one-third of patients), a clinically meaningful improvement in worst pain per BPI-SF was observed in both treatment groups. The BPI-SF is a questionnaire used to measure how pain affects a patient’s daily functioning in tasks like mood, walking ability, work, relationships, sleep and enjoyment of life. Those in the Padcev and Keytruda group experienced greater improvements in pain compared with those in the chemotherapy group.

The investigators also assessed changes in the EORTC Quality of Life Questionnaire (EORTC QLQ-C30), which measures global health status (GHS; overall patient wellbeing) and QOL.

Patients in the Padcev and Keytruda group demonstrated a worsening in GHS/QOL score at week 3, with a return to baseline at week 4. Patients in the chemotherapy group 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 Padcev and Keytruda group versus 3.2 months in the chemotherapy group.

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

Additionally, patients in the Padcev and Keytruda group demonstrated improved functioning across all functioning domains in the EORTC QLQ-C30 assessment compared with those in the chemotherapy group, assessed by a change from baseline to week 26.

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

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 [Padcev and Keytruda] for patients with locally advanced/metastatic urothelial cancer.”

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Padcev and Keytruda improve survival and progression among patients with bladder cancer, but don’t adversely impact pain, functioning or quality of life.

Padcev Plus Keytruda Doesn’t Worsen Quality of Life in Bladder Cancer

Xtandi plus Pluvicto improved PSA progression-free survival in certain patients with prostate cancer, research showed.

Patients with metastatic castration-resistant prostate cancer (mCRPC) experienced improved prostate-specific antigen (PSA) progression-free survival (PSA-PFS) when treated with Pluvicto (Lu-PSMA-617) and Xtandi (enzalutamide) compared with Xtandi alone, according to interim findings from the phase 2 ENZA-p study presented at the 

2023 European Society of Medical Oncology (ESMO) Congress

 as the time to two consecutive increases in PSA (a protein that is associated with the presence of prostate cancer in the body) of 50% and five or more nanograms/milliliter above nadir or death.

“This is the first randomized trial combining an androgen receptor signaling inhibitor, (Xtandi), with (Pluvicto). It provides strong evidence for an enhanced anti-cancer effect with the combination of (Xtandi) and (Pluvicto) based on the primary end point, PSA-PFS,” said Dr. Louise Emmett during an oral presentation of the findings at the ESMO 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 Xtandi alone. Median radiographic PFS was 16 months with the combination therapy compared with 12 months for Xtandi alone.

Further, PSA 50% (decrease of at least 50% from baseline) response rates were 93% (77 of 83 patients) in the combination arm, compared with 68% (54 of 79 patients) for Xtandi alone. PSA 90% (decrease of at least 90% from baseline) response rates were 78% (65 of 83 patients) among those in the combination arm compared with 37% (29 of 79 patients) among those who received Xtandi alone.

In total, the ENZA-p study included 162 patients with mCRPC. Patients were randomly assigned 1:1 to two groups: 79 patients were in the Xtandi alone group and 83 patients in the Xtandi plus Pluvicto group.

Those included in the combination therapy arm underwent two doses with Pluvicto with SPECT with two 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 four doses of Pluvicto.

Emmett commented in the presentation, “We used two to four doses of (Pluvicto) in the ENZA-p trial, but two to six doses may further improve progression-free survival, particularly in those patients who have a high proportion of androgen persistent clones.”

Serious side effects were reported in 28 of 79 patients (35%) who received Xtandi alone, compared with 27 of 81 patients (33%) who received Xtandi with Pluvicto. Grade 4 or 5 side effects were reported among three of 79 patients (4%) in the Xtandi monotherapy arm, compared with eight of 81 patients (6%) 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 overall survival (OS, the time a patient lives following treatment) in the study until July 2024.

Data presented at ESMO “provides strong evidence for an enhanced anti-cancer effect with the combination” of Pluvicto and Xtandi, according to one expert.

Hannah Clarke

Alternative Docetaxel Dosing Reduces Toxicity Risk in Prostate Cancer

Imfinzi Not Associated With Bladder Cancer Quality of Life Decline

Padcev Plus Keytruda Doesn’t Worsen Quality of Life in Bladder Cancer

Pluvicto Plus Xtandi Enhances Anti-Tumor Activity for Some Patients With Prostate Cancer

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