Drug combination boost PARP inhibitor response in resistant ovarian cancer

April 3, 2017

About one-third of patients with ovarian cancer who wouldn't be expected to respond to a PARP inhibitor had partial shrinkage of their tumor when a kinase inhibitor was added to treatment, report scientists from Dana-Farber Cancer Institute.

"When we combined the two drugs, we obtained a very good response rate - as high as 36 percent in patients with that was resistant to ," said Panagiotis Konstantinopoulos, MD, PhD, who presented the findings during a clinical trials mini-symposium on Sunday, April 2, 2017 at 3:00 p.m., at the annual meeting of the American Association for Cancer Research (AACR).

Twenty-eight patients with high-grade serous ovarian cancer received olaparib, a PARP inhibitor, along with an investigational alpha-specific PI3-Kinase inhibitor, BYL719, in the phase I trial. Twenty-six of the 28 had platinum-resistant cancer. In such patients, response to a PARP inhibitor itself is as low as 4 percent, said Konstantinopoulos, a medical oncologist with the Susan F. Smith Center for Women's Cancers at Dana-Farber.

In pre-clinical studies, adding a PI3K inhibitor appeared to sensitize the cancer cells to the effects of the PARP inhibitor, which impairs tumor cells' ability to repair DNA damage. The median duration of the response in the ovarian cancer patients was about 5.5 months, which is "a good duration of response in this patient population," said Konstantinopoulos. Five patients remained on treatment at the time of the presentation.

Olaparib is approved for treatment of platinum-resistant ovarian cancer in women with germline BRCA mutation. However, in the current trial, the response rate was 29 percent in women without germline BRCA mutations - not much lower than the rate of 33 percent in patients without the inherited BRCA mutations.

Overall, the combination was well tolerated, according to the report: Four patients discontinued therapy because of toxicity.

"The activity of this combination in ovarian without germline BRCA mutations and with platinum-resistant disease was higher than expected from olaparib monotherapy and warrants further investigation," said Konstantinopoulos.

Explore further: Niraparib significantly improves outcome of ovarian cancer patients in landmark trial

Related Stories

Niraparib significantly improves outcome of ovarian cancer patients in landmark trial

October 8, 2016
The PARP inhibitor niraparib significantly improves the outcome of platinum-sensitive recurrent ovarian cancer, according to full data from the ENGOT-OV16/NOVA trial presented for the first time at the ESMO 2016 Congress ...

Olaparib and PI3K inhibitor BKM120 combination active against ovarian and breast cancer subtypes

April 22, 2015
Combination treatment with the poly ADP-ribose polymerase (PARP) inhibitor olaparib and the investigational phosphatidylinositol-3-kinase (PI3K) inhibitor BKM120 was safe and yielded evidence of clinical benefit for women ...

Researchers use new imaging to show key enzyme in ovarian cancer

April 3, 2017
A new imaging test may provide the ability to identify ovarian cancer patients who are candidates for an emerging treatment that targets a key enzyme cancer cells need to survive. Currently, epithelial ovarian cancer patients ...

Olaparib shows promise in treating ovarian cancer, even without BRCA mutations

August 21, 2011
The PARP inhibitor, olaparib, that has shown promise in women with an inherited mutation in their BRCA1 or BRCA2 gene (accounting for about 5-10% of breast and ovarian cancer cases), has, for the first time, been shown to ...

Adding Veliparib to chemotherapy improved response rates among patients with BRCA-mutant breast cancer

December 8, 2016
Adding the investigational poly(ADP-ribose) polymerase (PARP) inhibitor veliparib to carboplatin and paclitaxel chemotherapy improved the overall response rate without increasing adverse events among patients who had locally ...

New, investigational PARP1/2 inhibitor BGB-290 shows promise

November 9, 2015
Treatment with BGB-290, a new, investigational, highly selective inhibitor of PARP1/2, was safe, tolerable, and yielded clinical responses in patients with advanced ovarian cancer, according to data from a phase I clinical ...

Recommended for you

Clear link between heavy vitamin B intake and lung cancer

August 22, 2017
New research suggests long-term, high-dose supplementation with vitamins B6 and B12—long touted by the vitamin industry for increasing energy and improving metabolism—is associated with a two- to four-fold increased lung ...

Study provides insight into link between two rare tumor syndromes

August 22, 2017
UCLA researchers have discovered that timing is everything when it comes to preventing a specific gene mutation in mice from developing rare and fast-growing cancerous tumors, which also affects young children. This mutation ...

Retaining one normal BRCA gene in breast, ovarian cancers influences patient survival

August 22, 2017
Determining which cancer patients are likely to be resistant to initial treatment is a major research effort of oncologists and laboratory scientists. Now, ascertaining who might fall into that category may become a little ...

Study identifies miR122 target sites in liver cancer and links a gene to patient survival

August 22, 2017
A new study of a molecule that regulates liver-cell metabolism and suppresses liver-cancer development shows that the molecule interacts with thousands of genes in liver cells, and that when levels of the molecule go down, ...

Zebrafish larvae could be used as 'avatars' to optimize personalized treatment of cancer

August 21, 2017
Portuguese scientists have for the first time shown that the larvae of a tiny fish could one day become the preferred model for predicting, in advance, the response of human malignant tumors to the various therapeutic drugs ...

Scientists discover vitamin C regulates stem cell function, curbs leukemia development

August 21, 2017
Not much is known about stem cell metabolism, but a new study from the Children's Medical Center Research Institute at UT Southwestern (CRI) has found that stem cells take up unusually high levels of vitamin C, which then ...

0 comments

Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.