Certain Patients with Prostate Cancer Continue to Tolerate Extended Nubeqa Treatment

Patients with nonmetastatic castration-resistant prostate cancer continued to tolerate long-term treatment with Nubeqa, allowing them to maintain their quality of life and remain on therapy.

Follow-up data of more than two years demonstrated that men with nonmetastatic castration-resistant prostate cancer continue to tolerate treatment with Nubeqa (darolutamide) combined with androgen deprivation therapy.

The data, which were presented during the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, were a follow-up to prior study results form the phase 3 ARAMIS trial.

Findings from that trial, which were presented in 2020, demonstrated that adding Nubeqa to androgen deprivation therapy was associated with a significant overall survival improvement compared to placebo and androgen deprivation therapy. Moreover, those results indicated that combining Nubeqa with androgen deprivation therapy significantly delayed the beginning of cancer-related symptoms, as well as the initiation of chemotherapy to treat the patient population.

Although treatment with Nubeqa — and other second-generation androgen receptor inhibitors — is associated with improved survival among these patients, long-term side effects may require patients to reduce their dosing and subsequently force patients to discontinue treatment.

As a result, the study authors conducted an extended follow-up of the phase 3 ARAMIS trial to measure long-term tolerability of the study drug.

“Almost all patients treated with (Nubeqa) were able to receive the full planned dose with no change between double-blind and open-label periods,” lead study author Dr. Karim Fizazi, a medical oncologist at Institut Gustave Roussy in France, said while presenting the findings. “And the majority of patients who required dose modifications subsequently reescalated to the full dose.”

The phase 3 ARAMIS trial was a randomized, double-blind study — meaning patients nor the researchers knew who received Nubeqa plus androgen deprivation therapy or placebo plus androgen deprivation therapy. At the time, 955 patients received study drug and 554 received placebo. However, the trial was unblinded at primary analysis, which meant that all patients could receive open-label Nubeqa.

Treatment tolerability was assessed every 16 weeks. Median time on treatment was 18.5 months in the Nubeqa double-blind group, 11.6 months in the placebo double-blind group, 25.8 months in the Nubeqa double-blind and open-label group and 11 months in the placebo crossover to Nubeqa open-label group. Of note, 170 patients switched from placebo to receive Nubeqa plus androgen deprivation therapy.

The study drug was well-tolerated over both the double-blind and open-label periods (98.9% of patients received the full-planned dose) and most patients who required dose modifications were able to resume the planned dose (Nubeqa 89.6%, placebo 89.7%). The discontinuation rate due to disease progression was lower in the study drug group compared to the placebo group during the double-blind period (12.5% vs 35.3%). It remained a similar number with extended treatment during the double-blind and open-label period (12.6%). Discontinuation due to side effects increased slightly from the double-blind period (9%) to the double-blind and open-label period (10.5%).

A modeling analysis showed a positive association between overall survival and maximum PSA decline, indicating that long-term treatment with Nubeqa delays disease progression and extends survival.

“Landmark sensitivity analysis of patients with PSA data at week 16 confirmed a positive association between PSA declines at week 16 and subsequent outcomes including overall survival,” said Fizazi. “Adjusting the landmark analyses for baseline covariates had little impact on best effect on overall survival.”

Treatment-related side effects lead to permanent discontinuation in 85 double-blind Nubeqa-treated patients (8.9%), 48 double-blind placebo-treated patients (8.7%), 100 double-blind and open-label Nubeqa-treated patients (10.5%) and eight in the double-blind-Nubeqa open-label crossover group (4.7%). The most common treatment-related side effects included, but were not limited to, deep vein thrombosis (blood clotting), high/low blood pressure, peripheral ischemia (impaired blood supply to the tissues) or vasculitis (inflammation of blood vessels); and abdominal discomfort/distension/pain, diarrhea, gastritis, nausea or small-intestine perforation.

These data demonstrate that patients can remain on treatment long-term and, according to Fizazi, indicate that extended Nubeqa treatment delays disease progression and extends survival in men with nonmetastatic castration-resistant prostate cancer.

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