INTRAPERITONEAL CHEMOTHERAPY HELPFUL IN BRCA+ OVARIAN CANCER 

Long-term results from 2 large studies confirm the superiority of intraperitoneal (IP) administration of chemotherapy over intravenous (IV) administration after surgery in patients with advanced ovarian cancer.

"We have known for some years that intraperitoneal administration may give superior results...but it is balanced by more toxicity," said Jubilee Brown, MD, associate professor of obstetrics and gynecology at the University of Texas M.D. Anderson Cancer Center in Houston.

The exciting thing about these data "is that at 10-year follow-up, the survival effects persist," she told Medscape Medical News.

The same chemotherapy is used (cisplatin and/or carboplatin plus paclitaxel), but the dosing schedule is a little different for the 2 different routes of administration. The IP route bathes the whole abdominal cavity in chemotherapy, so the drug surrounds the ovaries and stays in place for some time; however, this also increases exposure to the drug and can result in more intense adverse effects. In addition, IP is more difficult to administer than IV; it requires different technology and a specialized skill set, she explained.

As a result, there has been "quite a lag in the oncology community in adopting intraperitoneal administration for our patients," Dr. Brown told Medscape Medical News.

The new data come from a 10-year follow-up of patients taking part in Gynecologic Oncology Group (GOG) trials 114 and 172. They were presented at the Society of Gynecologic Oncology (SOG) 44th Annual Meeting on Women's Cancer, being held in Los Angeles, California.

After the 876 women from the 2 trials had undergone primary surgical cytoreduction, they were randomized to receive either IP or IV chemotherapy. There was a significant improvement in median overall survival with IP administration, compared with IV administration (61.8 vs 51.4 months; P = .0048).

"This is big news," said Dr. Brown, who acts as a spokesperson for the SGO. The committee reviewing the abstracts for the meeting felt that this study is the one that is most likely to change clinical practice and have an impact on patients, she noted.

The other finding is that "more is better, but even some cycles are useful," she said. Patients who completed 5 or 6 cycles of IP therapy had a 5-year overall survival of 59%, compared with 33% for those who completed 3 or 4 cycles and 18% for those who completed 1 or 2 cycles (P < .001).

The data were presented by Devansu Tewari, MD, director of gynecologic oncology for the Southern California Permanente Medical Group in Orange County, and assistant professor of obstetrics and gynecology at the University of California, Irvine.

"There is no question that IP therapy should be much more widely offered," Dr. Tewari said. He described IP therapy as a "potential life-saver," and added that "too many women do not receive an explanation of the advantages and disadvantages."

However, Dr. Tewari cautioned that IP therapy needs to be administered by a physician who has expertise in the treatment and can best manage the risks and adverse effects.

Selecting Patients for IP Treatment

In their analysis, Dr. Tewari and colleagues found that younger and healthier patients completed more cycles of IP.

Another analysis of data from one of the trials (the GOG 172 study) suggests that decreased expression of the BRCA1 protein could be used as a biomarker to identify patients who are most likely to respond to IP therapy. That analysis, led by Thomas Krivak, MD, from Magee-Womens Hospital of UPMC in Pittsburgh Pennsylvania, was published online March 5 in the British Journal of Cancer.

Of the 393 patients analyzed by Dr. Krivak's team, 204 had tumors with normal BRCA1 expression and 189 had tumors with aberrant BRCA1 expression.

The survival advantage of IP chemotherapy was only seen in the subset of patients with aberrantBRCA1 expression. In this subgroup, median overall survival was 84 months with IP and 47 months with IV (P = .0002).

There was no significant survival difference for IP and IV administration in patients with normal BRCA1expression (58 vs 50 months; P = .818).

Aberrant BRCA1 expression is an independent prognostic factor for better survival in women randomized to IP therapy (hazard ratio, 0.67; P = .032), Dr. Krivak and colleagues conclude.

"This research should allow us to target a particular group of ovarian cancer patients and give them an improved outlook by making a very simple change to their treatment," Dr. Krivak said in a statement.

Dr. Brown said that this is early evidence showing that this subgroup of patients might respond better, but it pushes us "to consider IP." However, she added that it is too early "to make that a firm recommendation."

"This is an important observation that may substantially influence clinical management — specifically, the decision to deliver or not deliver IP chemotherapy in ovarian cancer," said Maurie Markman, MD, national director for medical oncology at the Cancer Treatment Centers of America, clinical professor at Drexel University College of Medicine in Philadelphia, and Medscape video blogger for Markman on Oncology.

"It is critical to note that this has nothing to do with BRCA mutations," Dr. Markman noted. "Rather, the research deals with the amount of BRCA protein [present in the tumor]."

It looks like the BRCA protein is involved in DNA repair, he explained. When levels of this protein are low, the cancer appears to be unable to repair the additional damage that results from the more dose-intensive approach of IP administration. However, with high levels of the protein, the additional damage can be repaired, so for patients with high levels of BRCA protein in their tumor, there is no added benefit from the IP approach, he said.

Testing tumor tissue for BRCA protein levels is not currently routine, he told Medscape Medical News, "but it is my understanding that this would not be difficult to implement."

Br J Cancer. Published online March 5, 2013. Abstract

Society of Gynecologic Oncology (SOG) 44th Annual Meeting on Women's Cancer: Abstract 6. Presented March 9, 2013.