It may be safe to say that the development of PARP (Poly ADP-ribose polymerase) inhibitors has changed the treatment environment for ovarian cancer. That’s because the development extended the progression-free survival period and other prognoses of ovarian cancer patients.

After it was known that PARP inhibitors effectively block the growth of cancer genes detected by BRCA (Breast Cancer Susceptibility gene), the American Cancer Society (ACS) and the National Comprehensive Cancer Network NCCN) have recommended BRCA tests on those with high probability of ovarian and breast cancer occurrence due to family histories.

A PARP inhibitor most widely used in ovarian cancer patients with BRCA mutations in Korea is Lynparja (olaparib). Lynparza also began to receive insurance benefits in October last year.

Korea Biomedical Review met with Professor Kim Yong-beom of the Ob-Gyn Department at Seoul National University Bundang Hospital to hear about how the appearance of Lynparza has changed the treatment environment for the domestic ovarian cancer patients.

Ovarian cancer is intractable cancer with a high recurrence rate of 85 percent among epithelial ovarian cancer patients who have received primary treatment and the lower five-year survival rate of 64.5 percent than breast cancer (93.6 percent) and cervical cancer (80.5 percent).

Question: Could you explain the domestic treatment environment of ovarian cancer?

Answer: Among gynecological cancers, cervical cancer can be examined. It means we can know in advance the signs of future cancer On the other hand, ovarian cancer and endometrial cancer has no early screening method, and are found after symptoms occur. Among the two, endometrial cancer is detected earlier because it shows vaginal bleeding in the outbreak. However, ovarian cancer is slow to be found because there are no outward symptoms until patients’ stomach began to swell toward the end of the third stage

Among Korean diagnosed with ovarian cancer, those in the third or fourth phase account for 60-70 percent of the total. It means that there are many patients found in the terminal stage. It is difficult to treat and the cure rate is very low. Patients in the third and fourth stages are likelier to develop cancer again after being completely treated.

Q: If it is found in the third or fourth stage, physicians are highly likely to conduct a surgery, but the survival rate is low.

A: Until 2000, there had been prevalent opinions that they remove tumor by surgery only to the extent possible and conduct chemotherapy. However, this method failed to improve survival rates. Since the turn of the 2000, the treatment paradigm has changed to eliminate as much tumor as possible through surgery. Since then, the survival rate has improved. To this day, tumor reduction through removing it is the standard treatment.

The problem is that although the cancer was removed as much as possible by surgery, the treatment performance was not improved as much as desired.

According to a U.S. data, the five-year survival rate (after surgery) improved by only about 5 percent. Since then, they have started looking for new drugs.

Q: The drug thus found seems to be a PARP inhibitor. What role does PARP inhibitor play in the current ovarian cancer treatment environment?

A: Until the 1990s, toxic anticancer drugs called platinum-based anticancer drugs were mainly used. At this time, the treatment performance (objective treatment response rate) of ovarian cancer hovered around 30-40 percent. In the early 1990s, a new drug called Paclitaxel appeared, raising the treatment response rate to 70 percent. Since then, the drug had been used continuously, but it has not reduced the recurrence rate. Upon the turn of the 2000s, a drug called Avastin (bevacizumab) appeared, pushing the response rate once again, but recurrences remained frequent.

Of the 100 patients in the third and fourth stages, 75 percent can be treated if they receive good surgery and chemotherapy. However, most experience recurrence within five years. Only 10 percent of patients can expect complete recovery without recurrence for five years. Others are the cases where the treatment does not work or recur after treatment. If ovarian cancer recurs two years after, it can recur after one year in the second treatment and six months in the third treatment. Later, the drug-free intervals all but disappear. Therefore, it is very important to prevent recurrence in ovarian cancer. Against this backdrop, PARP inhibitors have shown long-term inhibitory effects. This has also been proven by data.

Q: It seems likely that more patients would have been treated since olaparib began to get insurance benefits. What changes have there been in the medical field over the past year or so?

A: Patients first need to undergo genetic tests to receive olaparib treatment because it can be used for BRCA mutation patients. BRCA mutation patients account for 15-20 percent of epithelial ovarian cancer patients. Among them, only those in the first phase or who respond to the secondary chemotherapy can receive the treatment. As only 65-70 percent of patients in phase three or four respond to the treatment, they do not account for a significant share of the total. However, what’s important is the good treatment has arrived for progressive ovarian cancer patients, in other words, those with not so good prognoses.

Q: What were olaparib’s real effects and patients’ responses to it?

A: There is a patient whose cancer has spread to lymph nodes around the lungs and bronchi due to the stage-four ovarian cancer. This is a case where the cancer did not disappear and showed partial remission even after chemotherapy. I've administered olaparib maintenance therapy since then, and by the time the patient entered the 14th month, the cancer did not progress or spread further, and the patient still lives in a well-maintained state. Had it not been the olaparib therapy, I think the patients might have had far higher chance of recurrence.

Q: Aside from the current reimbursement criteria, is there a group of patients who can benefit from additional application of insurance benefits to olaparib?

A: Currently, only patients with BRCA mutations are eligible for insurance benefits. However, there is a genetic mutation similar to BRCA. It is HRD (homologous recombination deficiency). HRD-positive patients can also see the effect of PARP inhibition. The effects are not as clear and powerful as those in BRCA mutation, but show effects comparable to the latter. In fact, there are reports that PARP inhibitors are effective when used in patients in the HRD-positive group

In order for olaparib benefits to be applied to these patients, the benefits for HRD tests should be preceded. BRCA mutation patients account for about 15-20 percent, but the eligible patients’ share exceeds 50 percent when HRD- positive patients are included. This means that 50 percent of patients with advanced ovarian cancer can use this drug. That explains why physicians maintain that PARP inhibition alone maintenance therapy should be applied to the HRD-positive patients. Some studies have also shown that it is more effective when bevacizumab and PARP inhibitors are used together. However, this is not subject to insurance benefits, either. Currently, the combination of bevacizumab and olaparib therapy should be used at the patient's expense. If necessary, I think it would be good to expand insurance benefits to that.

Q: What message would you like to give to ovarian cancer patients?

A: In the past, ovarian cancer was the “cancer of fear.” These days, ovarian cancer is turning into a sustainable disease except for very serious cases. Just as you live by controlling diabetes or high blood pressure, you can also control ovarian cancer. With this in mind, it is most important to work hard on treatment. Medical professionals also do not treat it in one way. There are many options for treating ovarian cancer. So, through sufficient discussion with your physicians, make a decision and receive treatment in most appropriate methods.