Yes, you heard it right. Molecularly targeted treatments were already available for breast cancer, ovarian cancer, gallbladder cancer and lung cancer, but there has been nothing for prostate cancer. With tremendous research on prostate cancer in the PARP-era, the results of a large clinical trial called PROFOUND, has demonstrated the disease can now be treated with a targeted therapy approach.
Metastatic, castrate-resistant prostate cancer (mCRPC) is an aggressive form of prostate cancer that keeps growing even when the amount of testosterone in the body is reduced to very low levels. In the past decade researchers have been looking for new treatment options to use for mCRPC.
In women, PARP-inhibitors such as olaparib and rucaparib are important targeted therapies for ovarian cancer and breast cancer cases with mutated BRCA1/2. Genetic alterations that affect DNA repair processes are common in these cases. It’s no accident that researchers have identified patients who have alterations in BRCA1/2 genes as ideal candidates for treatment with PARP inhibitors.
As a part of cellular machinery, BRCA proteins and certain PARP proteins play a pivotal role in homologous recombination repair, which is an integral part of DNA damage response. In BRCA1/2 mutations this response is hampered. By blocking the activity of PARP proteins, DNA damage response becomes dysfunctional in such cells. Thus, cancer cells die.
On 19 May 2020, US FDA approved olaparib for metastatic castration-resistant prostate cancer (mCRPC) in adult patients with
- deleterious germline mutation in HRR (homologous recombination repair) pathway or
- suspected deleterious germline mutation in HRR pathway or
- somatic mutation in HRR pathway
who have progressed following prior treatment with enzalutamide or abiraterone.
On 19 May 2020, US FDA also approved BRACAnalysis CDx test (Myriad Genetic Laboratories, Inc.) for selection of patients with mCRPC carrying germline BRCA1/2 alterations as companion diagnostic devices for treatment with olaparib.
Results from an international clinical trial TRITON2 found that men with advanced prostate cancer who have mutated BRCA1/BRCA2 genes can be treated successfully with a targeted therapy known as rucaparib. Based on the initial efficacy and safety results from TRITON2, on 15 May 2020, PARP inhibitor rucaparib in mCRPC patients with mutated BRCA1/2 has been granted accelerated approval by the US FDA.
Recent studies have shown that 20-30% of men with metastatic prostate cancer have genetic alterations that impair cellular DNA repair mechanisms. Approval of molecularly targeted therapy along with companion diagnostics in such rapid succession has strengthen the glimmer of hope in patients.
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