FDA Approves Lynparza for Certain Pretreated Patients with Metastatic Prostate Cancer

The Food and Drug Administration (FDA) has approved the targeted drug Lynparza (olaparib) for the treatment of men with metastatic castration-resistant prostate cancer that is driven by a homologous recombination repair (HRR) gene defect and has progressed following treatment with the novel hormonal drugs Xtandi (enzalutamide) or Zytiga (abiraterone acetate).

Lynparza has the green light for use in treating these patients whether their HRR defect is inherited or acquired. HRR defects make it difficult for cancer cells to repair their DNA once it’s been damaged. Lynparza, part of a family of drugs known as PARP inhibitors, capitalizes on that weakness and further inhibits DNA repair.

The approval is based on findings from the phase 3 PROfound trial, which showed that Lynparza induced a 66% reduction in the risk of disease progression or death compared with Zytiga or enzalutamide in patients with altered BRCA1, BRCA2 or ATM genes, which are involved in DNA repair. Across all patients in the trial, who had mutations in any of those three genes or 11 others associated with HRR problems, Lynparza demonstrated a 51% reduction in the risk of disease progression or death versus either of the antiandrogen drugs.

The median overall survival across the study’s whole population was 17.5 months with Lynparza and 14.3 months with Xtandi or Zytiga.

In the trial, 245 patients with alterations in BRCA1, BRCA2 or ATM — established markers of HRR problems — were studied in a group known as cohort A. The other group, cohort B, included 142 patients with an alteration in BARD1, BRIP1, CDK12, CHEK1/2, FANCL, PALB2, PPP2R2A, RAD51B/C/D, or RAD54L, all genes that have a limited association with DNA repair deficiency. Within each group, patients were randomized 2:1 to Lynparza or physician's choice of Zytiga plus prednisone or Xtandi.

In cohort A, the overall response rate (the proportion of patients who had a complete or partial response to therapy) was 33.3% with Lynparza compared with 2.3% with the hormonal therapies. The median time until pain progression had not yet been reached with Lynparza when data was collected, compared with 9.92 months for the hormonal agents; this represented a 56% reduction in the risk of pain progression. In this cohort, the median time until disease progression confirmed by radiographic imaging was 7.4 months and 3.6 months with Lynparza and hormonal therapy, respectively.

In cohorts A and B combined, the median time until disease progression via radiography was 5.8 months with Lynparza versus 3.5 months for Xtandi or Zytiga. The overall response rate was 21.7% and 4.5% with Lynparza and Xtandi/Zytiga, respectively.

The most common side effects that occurred in 20% of patients or more who took Lynparza were anemia (47%), nausea (41%), fatigue/weakness (41%), decreased appetite (30%) and diarrhea (21%). The most common serious side effects that occurred in 1% or more of patients who took Lynparza were anemia (22%), fatigue/weakness (3%), vomiting (2%), difficulty breathing (2%), urinary tract infection (2%), pulmonary embolism (2%), decreased appetite (1%), diarrhea (1%), back pain (1%) and nausea (%). A total of 18% of patients who were treated with Lynparza discontinued treatment due to side effects.

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