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FDA approves liquid biopsy as companion diagnostic for rucaparib in prostate cancer


The FoundationOne Liquid CDx pan-tumor liquid biopsy examines over 300 cancer-related genes in a patient’s blood sample to inspect for deleterious alterations.

The FDA has approved FoundationOneLiquid CDx for use as a companion diagnostic with the PARP inhibitor rucaparib (Rubraca), which is approved by the FDA for the treatment of patients with BRCA­ mutation–positive metastatic castration-resistant prostate cancer (mCRPC).1

The pan-tumor liquid biopsy test examines over 300 cancer-related genes in a patient’s blood sample to inspect for deleterious alterations. Foundation Medicine, the manufacturer of the diagnostic, reported in a press release that FoundationOneLiquid CDx is covered for eligible Medicare and Medicare Advantage beneficiaries.

Celestia S. Higano, MD

“Now that we have drugs that specifically benefit patients with BRCA mutations, the ability to identify who has these mutations is paramount,” Celestia S. Higano, MD, University of Washington School of Medicine, stated in a press release.2 “In contrast to tissue biopsy, a liquid biopsy is a blood-plasma test that is less invasive than a tissue biopsy for assessing germline or somatic BRCA mutations. The FDA’s approval of liquid biopsy tests represents a significant advancement for clinicians and patients to make timely decisions about treatment options.”

Mark Socinski, MD

Also commenting on the approval in a press release,1 Mark Socinski, MD, executive director (Thoracic Cancer) and medical oncologist at the AdventHealth Cancer Institute, Orlando, Florida, stated, “Liquid biopsies are becoming an increasingly important option to inform personalized treatment decisions for physicians treating certain advanced cancer patients who require minimally invasive solutions to genomic testing. This approval helps expand access to important genomic information needed for physicians to make more informed decisions about targeted treatment approaches for their patients and is another important step toward making comprehensive genomic testing a part of routine clinical cancer care.”

The FDA approved rucaparib in May 2020 for the treatment of patients with deleterious BRCA mutation (germline and/or somatic)–associated metastatic mCRPC who have been treated with androgen receptor (AR)–directed therapy and a taxane-based chemotherapy.

The approval was based on data from the phase 2 TRITON trial, in which the PARP inhibitor induced a confirmed objective response rate (ORR) per independent review of 43.5% in heavily pretreated patients with mCRPC and a deleterious BRCA alteration.3 The ORRs were similar, regardless of whether patients had germline or somatic alterations, or whether the alteration was BRCA1 or BRCA2. The investigators did report, however, that PSA response rate was higher among patients with BRCA2 alterations.

The open-label, multicenter, international TRITON2 study, enrolled male patients with mCRPC associated with 1 of 13 homologous recombination repair gene alterations. Patients had disease progression on androgen receptor (AR)–directed therapy and 1 prior taxane-based chemotherapy.

Overall, the efficacy and safety populations for TRITON2 included 115 BRCA-positive patients with or without measurable disease. The median patient age was 72 (range, 50-88), 74% of patients were white, and all except 2 patients had an ECOG performance status <2. The median baseline PSA was 61.1 ng/mL and 67% of patients had a Gleason score ≥8 at baseline. Across the population, 62 patients had measurable disease at baseline and 53 patients had nonmeasurable disease.

Prior AR–directed therapy included abiraterone acetate (Zytiga; 64.3%), enzalutamide (Xtandi; 71.3%), and apalutamide (Erleada; 2.6%). Overall, 36.5% of patients had received ≥2 AR-directed therapies. Regarding docetaxel, 14.8% had received the chemotherapy for castration-sensitive disease and 93.9% had received it for castration-resistant disease. Other prior therapies received included cabazitaxel (Jevtana; 7%), sipuleucel-T (Provenge; 10.4%), and radium-223 (Xofigo; 12.2%).

Patients were treated with rucaparib at 600 mg twice daily until radiographic progression or treatment discontinuation. Tumors were radiographically assessed every 8 weeks for 24 weeks, and then every 12 weeks. PSA assessments were performed every 4 weeks.

Twenty-seven (43.5%) of the 62 patients with measurable disease had confirmed ORRs per independent radiology review. The responses comprised 7 complete responses and 20 partial responses. Fifteen of the 27 responders had a duration of response ≥6 months. An additional 28 (45.2%) patients had stable disease, 6 had progressive disease, and 1 patient was not evaluable. Among all 115 patients, the confirmed PSA response rate was 54.8% (n = 63).

Regarding safety, 70 (60.9%) of the 115 patients experienced a grade ≥3 treatment-related adverse event (TEAE). The most common grade ≥3 TEAE was anemia/decreased hemoglobin (25.2%). TEAEs led to dose interruptions or reductions in 63.5% of patients, and discontinuations in 7.8% of patients. There was 1 patient TEAE-related death (acute respiratory distress syndrome).

The approval of rucaparib and other targeted treatments, along with emerging agents in the pipeline, has made physician-patient discussions of genomic testing essential in the field of metastatic prostate cancer, according to Neeraj Agarwal, MD.

Neeraj Agarwal, MD

"From a clinical perspective, I believe physicians should discuss tumor genomic profiling with every metastatic prostate cancer patient to inform the use of targeted and immunotherapies," Agarwal, director of the Genitourinary Oncology Program and professor of Medicine at the Huntsman Cancer Institute, Salt Lake City, Utah, stated in a press release.1 "This approval addresses the need for blood-based genomic testing options when tissue can be challenging to obtain."


1. FDA Approves Foundation Medicine's FoundationOne®Liquid CDx, a Comprehensive Pan-Tumor Liquid Biopsy Test with Multiple Companion Diagnostic Indications for Patients with Advanced Cancer. Posted August 26, 2020. https://bwnews.pr/3b0CZqQ. Accessed August 27, 2020.

2. FDA Approves FoundationOne® Liquid CDx To Serve As Rubraca® (Rucaparib) Companion Diagnostic To Identify Eligible Patients With BRCA1/2-Mutant, Metastatic Castration-Resistant Prostate Cancer (MCRPC). Posted August 26, 2020. https://bit.ly/3b1lCGe. Accessed August 27, 2020.

3. Abida W, Patnaik A, Campbell D, et al. Rucaparib in men with metastatic castration-resistant prostate cancer harboring a BRCA1 or BRCA2 gene alteration [published online August 14, 2020]. J Clin Oncol. doi: 10.1200/JCO.20.01035

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