Report on ESMO 2018 – Part Two

We recently returned from the European Society for Medical Oncology (ESMO) meeting where conference news highlighted the increased movement of targeted therapies and immunotherapies into adjuvant and early-stage cancer settings. Read our earlier report on combination therapy trials in melanoma, colon cancer and breast cancer, including triple-negative breast cancer. Here, we cover other targeted therapies.

 

New PARP inhibitor successes

 

Promising new data on PARP inhibitors from Clovis and AstraZeneca/Merck also took the spotlight at ESMO 2018.  

 

Joaquin Mateo, of the Vall d’Hebron Institute of Oncology, discussed results of the TRITON2 trial for prostate cancer.

Joaquin Mateo, of the Vall d’Hebron Institute of Oncology, discussed results of the TRITON2 trial for prostate cancer.

In early October, Clovis received “Breakthrough Designation” from the U.S. Food and Drug Administration for Rubraca (rucaparib) in prostate cancer. At ESMO, Clovis presented clinical results from its Phase 2 TRITON2 trial showing that Rubraca elicited an overall response rate of 44% in men with metastatic castration-resistant prostate cancer with a germline or somatic alteration in BRCA1, BRCA2, or 1 of 13 other homologous recombination repair (HRR) genes. In addition, Rubraca led to a 51% confirmed PSA response rate.

 

If Rubraca continues to show a durable response at 6 months, Clovis is likely to receive an accelerated approval and be the first to market with a PARP inhibitor for prostate cancer. Moreover, both patients and physicians focus on PSA levels in advanced prostate cancer, so the fact that Rubraca achieved a significant PSA-lowering effect will likely be important for Rubraca’s commercial success.

 

Furthermore, Clovis presented genomic profiling data from TRITON2, based on tumor tissue biopsy and plasma cell-free DNA (cfDNA) (liquid biopsy). The data suggest that cfDNA can be used to identify deleterious homologous recombination (HR) gene alterations less invasively than tumor tissue testing, and will likely help Clovis identify more patients for further clinical trials with Rubraca.

 

Kathleen Moore, of the Stephenson Cancer Center at the University of Oklahoma, presented the results of the  SOLO-1 trial for early-stage BRCA-positive ovarian cancer,

Kathleen Moore, of the Stephenson Cancer Center at the University of Oklahoma, presented the results of the SOLO-1 trial for early-stage BRCA-positive ovarian cancer,

AstraZeneca and Merck also reported positive results for their PARP inhibitor, Lynparza (olaparib) at ESMO. Data from the SOLO-1 trial, which studied Lynparza as frontline maintenance therapy in early-stage BRCA-positive ovarian cancer, showed a dramatic benefit of three years progression-free survival for those treated with the drug compared to those receiving placebo (60.4% PFS and 26.9% respectively). The overall survival data for Lynparza in ovarian cancer has not yet matured, but the researchers are hoping for an increased cure rate.

 

In the 2nd line, recurrent setting, when the disease is no longer considered curable, PARP inhibitors are approved to treat patients regardless of their BRCA status. AstraZeneca reported that at a median follow-up of 41 months, the risk of disease progression or death was 70% lower for Lynparza-treated patients than those receiving placebo.

 

Evidence for PARP inhibitors in the broader front-line setting beyond BRCA-positive patients is expected to come in 2019 from two trials that are recruiting patients regardless of their tumor mutation status. The PAOLA-1 trial of Lynparza plus Avastin in first line maintenance therapy is expected to release data in the first half of 2019, while Tesaro’s PRIMA study of Zejula (niraparib) in ovarian cancer patients with a worse prognosis is expected to release data at the end of 2019.

 

So far, PARP inhibitors have mainly shown value in patients with BRCA germline mutations, but the BRCA mutation is only found in a subset of patients.  Will PARP inhibitors find success in broader patient populations? We’ll be watching.