COMMENTARY

'Important' Progress in Gynecologic Cancers: ESMO 2017

Susana Banerjee, MBBS, MA, PhD, FRCP

Disclosures

November 03, 2017

Hello. My name is Dr Susana Banerjee. I am a consultant medical oncologist at the Royal Marsden Hospital in London, and I specialize in the treatment of gynecologic cancers.

Welcome to Medscape Oncology Insights, coming to you from the 2017 Congress of the European Society for Medical Oncology (ESMO). Today, we will be discussing some of the highlights of the gynecologic malignancy sessions at the meeting.

There have been exciting practice changes at ESMO Congress, and I am pleased to say that includes the gynecologic cancers. In my role as part of the gynecology faculty and also of the scientific committee of the ESMO gynecologic cancers track, I am going to summarize some of the key events here. There are several topics and presentations, and I really urge you to look at the ESMO website, as I will not be able to cover all of these, but I will give you a bit of a flavor of what has been going on.

PARP Inhibitors in Ovarian Cancer

We are in an era where poly(ADP)-ribose polymerase (PARP) inhibitors are changing the management of ovarian cancer. There are now three randomized phase 3 clinical trials, which have shown significant improvements in progression-free survival with PARP inhibitors as maintenance therapy after platinum-based chemotherapy in platinum-sensitive ovarian cancer.

Last year at ESMO 2016, the ENGOT-OV16/NOVA study on maintenance niraparib was presented and subsequently published in the New England Journal of Medicine. 1 This year at ESMO 2017, we heard the practice-changing results of the ARIEL3 study.2 Professor Ledermann and colleagues2 presented results of this phase 3 randomized study of maintenance rucaparib in platinum-sensitive ovarian cancer. This showed that there was a significant overwhelming improvement in progression-free survival with the addition of rucaparib as maintenance therapy versus placebo. This was not only in the germline BRCA-mutated population, but also the population of women who had homologous recombination deficiency, as well as the entire intention-to-treat population.

In the same session, there were the quality-of-life and patient-reported outcomes results of the ENGOT-O16/NOVA3 study. This is really important when we are taking these treatments to the clinics. This study, which I am the coauthor of, showed that there was no detrimental effect of niraparib treatment versus placebo.

Effects of the PARP inhibitor niraparib in an older population were also presented at the congress.4 We are living in an era with an aging population and where women with ovarian cancer may be older, and in particular when these drugs may be given to older patients without germline BRCA mutations, treating them is going to become more significant. This subset analysis showed that there were similar efficacy and toxicity in patients over the age of 70 years.

What is clear is that all three PARP inhibitors—rucaparib, olaparib, and niraparib—have excellent efficacy that is changing practice in the management of ovarian cancer. What is also becoming clear is that there are different toxicity and tolerability profiles among the three PARP inhibitors and, indeed, other PARP inhibitors in line.

What is really important is having real-world clinical experience of using these drugs so that we can inform clinicians and oncology professionals on how to manage patients on these drugs, including dose modifications and differing starting doses, and how we can improve the benefits to these patients by ensuring that they stay on treatment for the maximum beneficial time.

Dose-Dense Chemotherapy for Ovarian Cancer

Another important practice-confirming study is the ICON8 trial.5 The results of the primary analysis of the ICON8 trial, which was led by UK investigators, was presented by Dr Clamp and colleagues.5 This Gynecologic Cancer Intergroup (GCIG) phase 3 randomized trial is the largest trial addressing dose-dense weekly chemotherapy as first-line therapy for the treatment of ovarian cancer.

The Japanese study JGOG 30166 was published some time ago in Lancet Oncology and showed that there was an improvement in survival with a dose-dense approach. However, there were some concerns about whether there were ethnic pharmacodynamic differences. Therefore, it was important to address this topic in Caucasian patients and non-Japanese populations.

The ICON8 study demonstrated that dose-dense chemotherapy with weekly paclitaxel—either weekly paclitaxel with every-3-week carboplatin or weekly carboplatin with weekly paclitaxel—was not superior to every-3-week carboplatin/paclitaxel, which is the established standard of care. There was no difference in terms of progression-free survival, and the results are in keeping with two other important clinical trials—the US GOG-02627 and the Italian study MITO-7.8

Now we have three studies that confirm that every-3-week carboplatin/paclitaxel remains the standard of care, at least in the non-Japanese population. This is important in clinical practice.

Cervical Cancer

There have also been important presentations in cervical cancer, an area that needs much research.9 In recurrent metastatic cervical cancer, an early phase clinical trial of a novel agent called tisotumab10 showed very promising early results. This agent is an antibody/drug conjugate composed of a tissue-factor–specific monoclonal antibody conjugated to monomethyl auristatin E (MMAE), a chemotherapy. In this study, Vergote and colleagues10 reported a response rate of over 30%. This is important for a group of patients with an unmet clinical need, where treatment options are limited and response rates are very low. This clearly warrants further investigation in larger randomized clinical trials.

This was a very exciting meeting for gynecologic cancers, and I urge you to look at the many abstracts within this section that I have not had time to cover today.

I am very pleased to be the track chair for gynecologic cancer at ESMO 2018 in Munich. I look forward to reporting back to you then.

Thank you for joining me. This is Susana Banerjee, speaking from ESMO 2017 in Madrid, Spain.

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