New combination therapy shows promising results for prostate cancer

A novel combination prostate cancer therapy has been approved by the US Food and Drug Administration.

The new treatment combines two Pfizer-produced cancer drugs, Xtandi (also known as enzalutamide) and Talzenna (which also goes under the name talazoparib).

While Xtandi is a medication typically used for prostate cancer, the addition of Talzenna – an oral poly ADP-ribose polymerase (PARP) inhibitor – is new in patients with the disease.

The FDA approval specifically applies to adults with homologous recombination repair (HRR) gene-mutated metastatic castration-resistant prostate cancer (mCRPC).

This type of cancer has spread beyond the prostate gland and progressed despite surgery and other treatment to lower testosterone.

Approximately 10%-20% of patients with prostate cancer develop mCRPC within five to seven years of diagnosis. HRR gene mutations are found in approximately 25% of tumours from men with mCRPC and have been associated with aggressive disease and poor prognosis.

In a phase 3 TALAPRO-2 trial, this drug combination was found to decrease the risk of cancer progression by 55%, compared to the standard treatment in these patients for whom the FDA approved the combination.

Neeraj Agarwal. Image: Huntsman Cancer Institute

Neeraj Agarwal, Presidential Endowed Chair of Cancer Research at Huntsman Cancer Institute at the University of Utah and global lead investigator for TALAPRO-2, said: “Despite treatment advancement in metastatic castration-resistant prostate cancer, the disease can progress quickly, and many patients may only receive one line of therapy.

“Therefore, new first-line treatment options are needed to reduce the risk of disease progression or death. For patients with mCRPC harbouring HRR genetic alterations, outcomes are even worse.

“The FDA’s approval of the talazoparib and enzalutamide combination is based on the findings from the pivotal TALAPRO-2 study, which demonstrated statistically significant and clinically meaningful reductions in the risk of progression or death among HRR gene-mutated tumours in patients with metastatic castration-resistant prostate cancer.

“It represents a treatment option deserving of excitement and attention.”

The approval came just days after he published the findings of the study in The Lancet, as the lead author, a first in institutional history.

The Phase 3 TALAPRO-2 trial is a two-part, two-cohort, multicentre, randomised, double-blind, placebo-controlled study that included two patient cohorts.

The safety of Talzenna and Xtandi in the TALAPRO-2 trial was generally consistent with the known safety profile of each medicine. Serious adverse reactions occurred in 30% of patients treated with Talzenna plus Xtandi. Serious adverse reactions reported in more than 2% of patients included anaemia (9%) and fracture (3%). Discontinuation of Talzenna occurred in 10% of patients.

A marketing authorisation application (MAA) for the Talzenna and Xtandi combination has been accepted for review by the European Medicines Agency. Pfizer has also shared data with other regulatory agencies to support regulatory filings.

Angela Hwang, chief commercial officer, president, global biopharmaceuticals business, Pfizer, said: “Pfizer has a legacy of bringing medicines to patients with genitourinary cancers and helping improve outcomes for patients suffering from advanced prostate cancer.

“As a global standard of care, Xtandi has shown efficacy in three types of prostate cancer, and the addition of Talzenna demonstrated significant improvements in delaying or preventing radiographic progression-free survival or death in patients with this type of advanced prostate cancer.”

She added that with the FDA’s approval of Talzenna plus Xtandi “we are proud to be able to offer this potentially practice-changing treatment to patients and add to their options in managing this aggressive disease.”

Prostate cancer is one of the most common types. Around one in eight men will be diagnosed with it in their lifetime.

According to the American Cancer Society, about six cases in 10 are diagnosed in men who are 65 or older, and it is rare in men under 40.

Neli Ulrich, chief scientific officer and executive director of the Comprehensive Cancer Center at Huntsman Cancer Institute, said: “This work, led by Dr Agarwal, with colleagues across the world, is absolutely ground-breaking. It will make a big difference in treatment options for many prostate cancer patients.”