COMMENTARY

Gynecologic Cancers: New Regimens, Predictive Biomarkers

Maurie Markman, MD

Disclosures

May 22, 2015

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Hello. I'm Dr Maurie Markman from Cancer Treatment Centers of America in Philadelphia. I want to briefly discuss a number of highly provocative abstracts that are going to be presented in the gynecologic cancer arena at the 2015 American Society of Clinical Oncology (ASCO) meeting.

There are several papers that have specifically looked at the addition of a third agent, a carboplatin plus paclitaxel (CP), in the management of metastatic or recurrent endometrial cancer. One abstract of a randomized phase 2 trial[1] suggested that the addition of bevacizumab to CP can improve progression-free survival (PFS) in this clinical setting.

However, a randomized phase 2 study[2] from the Gynecologic Oncology Group questions that finding, so this particular observation and discussion should be very interesting.

An interesting follow-up study on the TRINOVA-1 trial,[3] looking at a novel antiangiogenic agent plus weekly paclitaxel, demonstrated no improvement in overall survival (OS) in the overall patient population intention to treat. But, in the subset of patients with ascites, there did appear to be, in this analysis, an improvement in OS. It would be interesting to hear the discussion in that setting.

There also was a very interesting analysis in the ARIEL2 trial,[4] which was a prospective attempt to identify ovarian cancer patients likely to respond to rucaparib. It demonstrated, not surprisingly, that patients with a BRCA mutation had a high response rate. In addition, a particular signature was found that also suggested a high response rate in the non-BRCA-mutated patient population. Approximately 32% of patients with that signature responded. That compares with a population that did not have this genetic signature and a BRCA wild type, where response rate was only 11%. Again, discussion of this particular finding would be very interesting.

A novel compound that has been shown or is suggested to have activity in a TP53-mutant ovarian cancer was examined in a randomized phase 2 trial,[5] specifically in patients with TP53 mutations. This trial demonstrated an improvement in PFS in this randomized phase 2 setting. This obviously suggests that it would be very interesting to further follow up with a randomized phase 3 trial looking at PFS as a primary endpoint, with OS as a secondary endpoint

There will also be an interesting presentation of a retrospective analysisof possible candidate-predictive biomarkers for bevacizumab's benefit or lack of benefit, based upon data from the previously published GOG-0218 trial.[6] This will be a very interesting look at the ability to find a biomarker to determine whether this drug makes sense in the frontline setting.

And finally, there will be several reports looking at immunotherapy with the new, highly effective immunologic agents that have been shown to have activity in lung cancer and melanoma. Early trials are now looking at activity in ovarian cancer, and they will be presented in several sessions. This is obviously going to be provocative. Again, quite early data, but certainly it might lead one to see a need or desire to have this very exciting class of drugs tested further in the gynecologic cancer arena.

I encourage you, if you have an interest in gynecologic cancers, to attend the sessions at ASCO dealing with these cancers. Or, if time does not permit because of many other exciting sessions, then certainly view the abstracts. Read the abstracts and then possibly see the actual presentations online at a later date.

Thank you for your attention. Enjoy the meetings in Chicago.

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