Sabrina Serani

Nubeqa/ADT treatment led to positive impacts on HRQoL vs placebo in mHSPC: © stock.adobe.com.

Among patients with with metastatic hormone-sensitive prostate cancer (mHSPC), Nubeqa (darolutamide) and androgen deprivation therapy (ADT) treatment led to positive impacts on health-related quality of life (HRQoL) when compared with placebo and ADT, according to patient-reported outcome data from the phase 3 ARANOTE trial.

Notably, these data, which were shared at the

, also highlighted clinically meaningful delays in pain progression with the investigative treatment.

Furthermore, on June 3rd, 2025, just days after the data was presented at the meeting, the United States Food and Drug Administration 

(FDA) granted approval to Nubeqa for the treatment of patients

 with mHSPC based on data from the ARANOTE study.

“[This] is the first and only androgen receptor antagonist to demonstrate clinically meaningful delays in pain progression and overall well-being, including those specific areas of social and family well-being, functional well-being, and urinary symptoms. Health-related quality of life benefits may be greatest in patients treated with Nubeqa who had ultralow [prostate-specific antigen (PSA)] levels,” explained Dr. Alicia Morgans, in a presentation of the study

Morgans, a genitourinary medical oncologist who serves as the director of the Survivorship Program at Dana-Farber Cancer Center and associate professor of Medicine at Harvard Medical School, in Boston.

In this analysis, multiple patient-reported outcome measures were used to assess patient experience during treatment. They included the Brief Pain Inventory Short Form (BPI-SF), used to assess pain, specifically the worst pain in the past 24 hours, and the Functional Assessment of Cancer Therapy-Prostate (FACT-P) total score, a questionnaire evaluating overall quality of life in patients with prostate cancer. The FACT-P includes domains such as physical well-being, social and family well-being, emotional well-being, functional well-being, and prostate cancer-specific assessments, including bowel and urinary difficulties.

The analysis showed that Nubeqa was associated with a delay in pain progression, defined as the time from randomization to a confirmed increase of at least 2 points in worst pain over the nadir or the initiation of opioid treatment for at least 7 days versus placebo. When assessing time to pain progression by PSA response, patients who reached a PSA of less than 0.02 or 0.2 nanograms per millilitre (ng/mL) at any time had a longer time to pain progression than patients with a PSA greater than or equal to 0.2 ng/mL.

“I think this is a critical thing for us to recognize that our patients’ quality of life, intuitively, of course, is associated with disease control. But this is also helpful for us in clinical practice so that we can encourage patients as their cancer appears to be better controlled; we expect them to feel better,” Morgans explained during the presentation.

Regarding time to FACT-P deterioration, Nubeqa was associated with an extension in median time to deterioration, defined as the first decrease of 10 or more points in the total score, by 5.1 months versus placebo. Improvements were most prominent in the areas of social and family well-being, functional well-being, and prostate cancer concerns, including urinary symptoms. Similarly with the BPI-SF, patients with a PSA of 0.02 or 0.2 ng/mL at any time had a longer time to HRQoL deterioration versus a PSA of 0.2 ng/mL or greater.

The phase 3 ARANOTE trial assessed Nubeqa plus ADT versus placebo and ADT for the treatment of mHSPC. 

2024 European Society of Medical Oncology (ESMO) Congress

 showed that the combination reduced the risk of radiographical progression or death by 46% and demonstrated a favorable safety profile.

 for the study combination in patients with mHSPC in November, 2024.

the 2025 ASCO Genitourinary Cancers Symposium

A total of 669 patients enrolled globally were randomly assigned on a 2:1 basis to receive Nubeqa 600 mg twice daily plus ADT (446 patients) or placebo plus ADT (223 patients). The primary end point was radiographic progression-free survival by central blinded review, with secondary end points including overall survival, time to PSA progression, and safety.

At a data cutoff of June 7, 2024, the median follow-up was 25.3 months for the Nubeqa group and 25.0 months for the placebo group. The median radiographic progression-free survival for Nubeqa plus ADT was not reached compared with 25.0 months for placebo plus. At 24 months, the rate of radiographic progression-free survival was 70.3% for the Nubeqa group versus 52.1% for the placebo group.

The median treatment duration was 24.2 months in the Nubeqa group compared with 17.3 months for the placebo group. Incidence of treatment-emergent side effects was similar between the arms, with 91.0% any-grade and 30.8% grade 3 (severe) or 4 (life-threatening) treatment-emergent side effects with Nubeqa plus ADT and 90.0% any-grade and 30.3% grade 3 or 4 with ADT plus placebo.

“Health-related quality of life (HRQoL) outcomes with darolutamide in the phase 3 ARANOTE trial” by Dr. Moregans, et al. 

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Articles

Nubeqa (darolutamide) combined with androgen deprivation therapy (ADT) significantly improved health-related quality of life (HRQoL) in patients with metastatic hormone-sensitive prostate cancer (mHSPC) compared to placebo and ADT, as demonstrated in the phase 3 ARANOTE trial. The treatment delayed pain progression and was associated with better social, family, and functional well-being. Following these findings, the FDA approved Nubeqa for mHSPC. The trial also showed a 46% reduction in radiographic progression or death risk, with a favorable safety profile and extended radiographic progression-free survival.

Nubeqa and ADT treatment led to positive impacts on health-related quality of life vs placebo in metastatic hormone-sensitive prostate cancer. 

Nubeqa Combo Positively Impacts HRQoL vs Placebo in Prostate Cancer Subgroup 

Treatment with Herceptin (trastuzumab) and Perjeta (pertuzumab) with endocrine therapy but without chemotherapy has been shown to potentially be an effective treatment for patients with HER2-positive and hormone receptor (HR)-positive metastatic breast cancer. Furthermore, the addition of Kisqali (ribociclib) might improve patient outcomes even more.

These findings come from the second interim efficacy analysis of the phase 3 DETECT V trial presented at the 2024 ESMO Congress.

In the study, 270 patients with metastatic HR/HER2–positive breast cancer receiving a first to third line of treatment were randomized to one of two arms. In the chemotherapy arm, patients received physician’s choice of chemotherapy plus Herceptin/Perjeta followed by maintenance Herceptin/Perjeta and endocrine therapy. In the chemotherapy-free arm, patients received physician’s choice of endocrine therapy plus Herceptin/Perjeta. After 124 patients enrolled, the study was amended to add Kisqali to endocrine therapy in both arms. 

The combination of Herceptin, Perjeta, and endocrine therapy without chemotherapy showed promising results in patients with HR+/HER2+ metastatic breast cancer.

Adding Kisqali to the treatment regimen further improved patient outcomes, reducing the risk of disease progression or death.

The DETECT V trial suggests that a chemotherapy-free regimen with Herceptin, Perjeta, and endocrine therapy, potentially with the addition of Kisqali, may be a promising treatment option for patients with HR+/HER2+ metastatic breast cancer.

Overall survival (OS, the time a patient lives, regardless of disease status) and progression-free survival (PFS, the time a patient lives without their disease spreading or worsening) was similar between the arms. In the chemotherapy-free arm, the median OS was not reached (meaning more than half of the patients in that arm were still alive) versus 46.1 months in the chemotherapy arm. For PFS, the median was 19.1 months in the chemotherapy-free arm versus 22.4 months in the chemotherapy arm.

The addition of Kisqali improved PFS and OS, with patients treated with Kisqali being 48% less likely to experience disease progression or death and being 58% less likely to die of any cause.

Dr. Wolfgang Janni emphasized that this was a comparison of subsequent study cohorts, not a randomized comparison for the addition of Kisqali. Janni is a professor at the University of Ulm in Ulm, Germany.

Regarding safety of the chemotherapy versus chemotherapy-free arms, the most common side effect in both arms was diarrhea, with 100 all-grade incidences in the chemotherapy-free arm and 146 in the chemotherapy arm.

“We did observe a higher amount of diarrhea in the chemotherapy containing arm, while we saw more prolonged neutropenia [low count of neutrophils, a type of white blood cell] in the chemo[therapy]-free arm, possibly due to longer exposure to [Kisqali],” Janni explained. In the chemotherapy-free arm, there were 64 incidences of all-grade neutropenia and 48 grade 3 (severe) or higher.

For the safety analysis of Kisqali versus no Kisqali, 55 patients (37.4%) receiving Kisqali experienced at least one serious side effect versus 43 patients (34.7%) in the no Kisqali arm. Ninety-five patients (64.6%) and 62 patients (50%) in the Kisqali and no Kisqali arms, respectively, experienced at least one grade 3 or higher side effect.

“The tolerability comparison between the two cohorts did not show a difference in the overall incidence of serious [side effects], but in [side effects] with grade 3 or higher, which was mainly caused by the higher incidence of neutropenia and liver enzyme abnormalities in the [Kisqali] cohort. There were no treatment-associated deaths in this study,” Janni said.

The final results from this study are pending, as are longer-term findings from the Kisqali cohort, which had shorter follow-up due to its later addition into the study regimens.

Among patients with HR+/HER2+ breast cancer, Herceptin and Perjeta plus endocrine therapy proved to be beneficial without chemotherapy.

Herceptin, Perjeta Regimen May Be Effective Without Chemo in Breast Cancer

A treatment combination of Imjudo (tremelimumab) and Imfinzi (durvalumab) demonstrated improved survival outcomes, including disease control and treatment responses in patients with unresectable (surgically unremovable) hepatocellular carcinoma (liver cancer), according to a presentation at the 

The presentation highlighted updated five-year data from the phase 3 HIMALAYA study. These results set new standards in unresectable liver cancer, with one in 5 patients alive at five years, Dr. Lorenza Rimassa said in the presentation. 

A combination treatment of Imjudo (tremelimumab) and Imfinzi (durvalumab) has shown improved survival outcomes in patients with unresectable liver cancer.

The phase 3 HIMALAYA study revealed that one in five patients treated with Imjudo plus Imfinzi were alive at five years, surpassing the 9.4% survival rate for those treated with Nexavar.

Patients in the Imjudo plus Imfinzi group experienced a median overall survival of 16.43 months compared to 13.77 months in the Nexavar group.

The Imjudo plus Imfinzi combination also demonstrated better disease control, with higher rates of complete and partial responses and lower rates of disease progression.

Rimassa is an associate professor of medical oncology at Humanitas University and head of the Hepatopancreatobiliary Oncology Department at Istituto di Ricovero e Cura a Carattere Scientifico Maugeri Humanitas Research Hospital in Milan, Italy.

“This five-year updated analysis of the HIMALAYA study presents the longest follow-up to date in phase 3 studies for [unresectable liver cancer],” Rimassa said. “[Imjudo plus Imfinzi] sustained an overall survival (OS; time patients live, regardless of disease status) benefit versus [Nexavar (Nexavar)] and demonstrated unprecedented long-term survival benefit at five years, with a five-year survival rate of 19.6% for [Imjudo plus Imfinzi] versus 9.4% for [Nexavar].”

Survival Benefits of Imjudo Plus Imfinzi Versus Nexavar in Unresectable Liver Cancer

A total of 1,171 patients were randomly assigned to three treatment groups. The Imjudo-Imfinzi combination group included 393 patients. There were 389 patients in the Imfinzi monotherapy group and patients 389 patients in the Nexavar group. In the study, 393 patients were treated with the Imjudo-Imfinzi combination and 389 patients received Nexavar.

Patients from the Imjudo-Imfinzi combination group compared with Nexavar sustained an OS benefit. Specifically, the median OS was 16.43 months in the combination group and 13.77 in the Nexavar group. The median follow-up duration was 62.49 versus 59.86 months, respectively.

For patients experiencing disease control, the OS was enhanced, showing rates of 28.7% in the Imjudo-Imfinzi combination group and 12.7% in the Nexavar group at five years and increasing over time. There were 12 patients (3.1%) in the Imjudo-Imfinzi combination group who achieved complete response (disappearance of cancer) versus no patients in the Nexavar group, and 67 patients (17.0%) experienced partial response (tumor shrinkage) versus 20 patients (5.1%), respectively. Stable disease was achieved by 157 (39.9%) in the Imjudo-Imfinzi combination group and 216 patients (55.5%) in the Nexavar group, and 141 patients (35.9%) versus 118 (30.3%), respectively, experienced disease progression.

“More patients treated with [Imjudo-Imfinzi combination] versus Nexavar were still alive, still on study treatment, and fewer received a subsequent therapy at five years,” Rimassa noted.

Patients receiving the Imjudo-Imfinzi combination also experienced deeper tumor responses, including over 50% shrinkage in 34 patients, which was associated with longer overall survival, compared with 12 patients receiving Nexavar. In addition, 80 patients in the Imjudo-Imfinzi combination group versus 114 patients in the Nexavar group experienced minor responses of less than 30% tumor shrinkage; however, this also led to a long-term survival benefit for those receiving Imjudo-Imfinzi combination. In the Imjudo-Imfinzi combination group, there were 168 patients who had no shrinkage or growth versus 169 patients in the Nexavar group.

Rimassa stated that there were no new serious treatment-related side effects after the primary analysis with a data cut-off on Aug. 27, 2023. At the five-year data cut-off of March 1, 2024, 17.5% of patients in the Imjudo-Imfinzi combination group had experienced serious treatment-related side effects, which was the same percentage reported at the primary analysis. Similarly, for the Nexavar group, at the five-year analysis at the data cut-off, there were 9.9% of patients who experienced serious treatment-related side effects versus 9.4% at the primary data cut-off.

There were also 24.8% of patients in the Imjudo-Imfinzi combination group that had serious non-treatment-related side effects at the five-year data cut-off versus 23% at the primary data cut-off, and in the Nexavar group, there were 20.3% of patients experiencing serious non- treatment-related side effects versus 20.3%, respectively.

“Overall survival benefit with [the Imjudo-Imfinzi combination] was enhanced in patients who achieved disease control. Any degree of tumor shrinkage was linked to long-term survival, with those experiencing deep responses showing the greatest benefit. These findings indicate that conventional response measures such as complete response or partial response … may not fully capture the benefits of [the Imjudo-Imfinzi combination],” Rimassa concluded.

In patients with unresectable liver cancer, treatment with Imjudo plus Imfinzi showed better survival outcomes compared with Nexavar.

Imjudo Plus Imfinzi Improve Survival Versus Nexavar in Liver Cancer

A treatment combination of Braftovi (encorafenib), Erbitux (cetuximab) and chemotherapy showed promising anti-tumor activity in patients with BRAF V600E-mutant metastatic colorectal cancer who were previously treated with at least one line of systemic therapy, according to a presentation at the 

A presentation at the conference highlighted updated safety results from the phase 3 BREAKWATER study, which included three components: a safety portion, a phase 3 randomization and a second randomization labeled as cohort 3.

The safety portion included two cohorts: Braftovi plus Erbitux and FOLFIRI chemotherapy (cohort 1); and Braftovi plus Erbitux and mFOLFOX6 chemotherapy (cohort 2). The phase 3 component randomized patients to three treatment groups: Erbitux alone; Erbitux plus mFOLFOX6 chemotherapy; or the control group of three chemotherapy regimens: FOLFIRI, mFOLFOX6, or capecitabine and oxaliplatin (CAPOX) with or without Avastin (bevacizumab). Cohort 3 randomly assigned patients to either Erbitux/FOLFIRI chemotherapy or FOLFIRI chemotherapy with or without Avastin.

A treatment combination of Braftovi, Erbitux and chemotherapy showed promising anti-tumor activity in patients with BRAF V600E-mutant metastatic colorectal cancer.

Among previously treated patients receiving Braftovi, Erbitux and chemotherapy as a second-line therapy, the ORR was 44.4%.

In patients receiving Braftovi, Erbitux and chemotherapy as a second-line therapy, the median DOR was 12.5 months, the median PFS was 12.6 months, and the median OS was 19.7 months.

Patients must have confirmed stage 4 colorectal cancer and be ineligible if they have tumors that are microsatellite instability-high or mismatch repair-deficient.

Of note, the presentation of the BREAKWATER study at ESMO mainly focused on the safety portion, which included patients from cohort 1.

There were 30 patients enrolled in cohort 1. The median age was 56.5 years and 66.7% were men. The ECOG performance status was either 0 (ability to independently perform daily tasks; 73.3%) or 1 (ability to perform most daily tasks independently; 26.7%). Twelve patients had not received prior therapy, and 18 patients had one prior line of therapy.

In a presentation at the 2024 ESMO Congress, Dr. Josep Tabernero, head of the Department of Medical Oncology, Vall d’Hebron University Hospital and director of the Vall d’Hebron Institute of Oncology in Barcelona, Spain, discussed findings from the trial. Tabernero reported that only one dose-limiting toxicity (DLT; side effects from drugs that prevent an increase in dose) occurred with the Erbitux/chemotherapy combination, which was grade 4 (life-threatening) neutropenia (lower levels of a white blood cell type) that lasted more than seven days.

Treatment-related side effects of any grade were experienced by 93.3% of patients, with 50% of patients experiencing grade 3 (severe)/4 treatment-related side effects, and 16.7% of patients experiencing a serious side effect related to study treatment. There were no deaths related to the study treatment.

Efficacy data showed an objective response rate (ORR; percentage of patients whose cancer shrunk or disappeared) of 83.3% in patients from cohort 1 receiving Braftovi, Erbitux plus chemotherapy in the first-line metastatic setting. There were two complete responses (CRs; disappearance of cancer), eight partial responses (PRs; cancer shrunk) and one patient with stable disease (SD; cancer did not improve or worsen). The median duration of response (DOR) was not estimable. The median progression-free survival (PFS; time patients are alive without their disease worsening) was not evaluable, meaning not enough patients had their disease worsened by the data collection date, and the median overall survival (OS; time patients live regardless of disease status) was not evaluable.

Among previously treated patients from cohort 1 receiving treatment as a second-line therapy, the ORR was 44.4%. There was one CR, seven PRs and seven patients with SD. The median DOR was 12.5 months. The median PFS was 12.6 months, and the median OS was 19.7 months.

“The combination of [Braftovi, Erbitux] plus chemotherapy was tolerable without new safety signals in patients with BRAF V600E-mutant metastatic colorectal cancer … [and] showed promising improvement in key efficacy measures,” said Tabernero.

The BREAKWATER trial assessed the combination of Braftovi and Erbitux with or without chemotherapy in patients with metastatic colorectal cancer. Patients must have confirmed stage 4 colorectal cancer harboring a BRAF V600E mutation. Patients were ineligible if they had tumors that are microsatellite instability-high or mismatch repair-deficient.

Safety Among Patients With Metastatic Colorectal Cancer

At the 2024 ESMO Congress, Tabernero shared data from cohort 1 of the safety portion, which evaluated the combination of Braftovi, Erbitux and chemotherapy. The primary goal of the safety portion of the trial was DLTs, with secondary goals including safety and antitumor activity. 

Additional safety data showed that all patients experienced treatment-emergent side effects, with 63.3% and 46.7% experiencing grade 3/4 treatment-emergent side effects and serious treatment-emergent side effects, respectively. Treatment-emergent side effects leading to dose reduction, dose interruption or permanent discontinuation of any drug occurred in 53.3%, 73.3% and 30% of patients, respectively. Treatment-emergent side effects were associated with two patient deaths.

Treatment-emergent side effects across all grades occurring in at least 30% of patients included nausea (50%), diarrhea (46.7%), constipation (43.3%), fatigue (43.3%), dermatitis acneiform (acne-like bumps; 40%), rash (33.3%) and skin hyperpigmentation (30%). Treatment-emergent side effects of grade 3 or worse included two cases of dermatitis acneiform and one case each of diarrhea, constipation and fatigue.

Erbitux combination is currently approved by the FDA

 for use in patients previously treated for BRAF V600E-mutated metastatic colorectal cancer.

“Currently, there are no specifically targeted first-line treatments for BRAF V600E-mutant metastatic colorectal cancer, which highlights the unmet need for novel treatment options for this patient population,” said Tabernero.

In his concluding remarks, Tabernero said, “These results support the continued evaluation of Erbitux plus chemotherapy as a treatment option for patients with BRAF V600E-mutated metastatic colorectal cancer in cohort 3 of the BREAKWATER study.”

In patients with BRAF V600E-mutant metastatic colorectal cancer, a combination of Braftovi, Erbitux and chemotherapy showed promising antitumor activity.

Sabrina Serani

Nubeqa Combo Positively Impacts HRQoL vs Placebo in Prostate Cancer Subgroup

Herceptin, Perjeta Regimen May Be Effective Without Chemo in Breast Cancer

Imjudo Plus Imfinzi Improve Survival Versus Nexavar in Liver Cancer

Braftovi Regimen Is Promising in Metastatic Colorectal Cancer

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