Combination Therapy Use in Ovarian Cancer

Robert L. Coleman, MD:Now the patient has presented with a fair amount of disease in the abdominal cavity and she has ascites. The thought is, “Okay, so now we know that she’s had this Q3-weekly schedule of paclitaxel in front-line setting with carboplatin and has developed this new disease, which has been associated with ascites.” Our options now are to think about nonplatinum-based regimens. Although I don’t like the terms platinum-sensitive and platinum-resistant, I think the point is that the timeframe for this disease to present the way it did would suggest that platinum is probably not going to be an effective agent in and of itself. Paclitaxel, though it was given before, has been used frequently in this case, when it’s been fractionated.

I mentioned that weekly paclitaxel was shown to be beneficial—in fact, potentially even more beneficial than Q3-weekly paclitaxel in the front-line setting. In the recurrent setting, it seems to have activity that’s at least as good as some of the other nonplatinum agents that would be appropriate for her. And there are many that would be appropriate for her, including liposomal doxorubicin, topotecan, gemcitabine—sometimes, I give that also in combination with cisplatinum—and paclitaxel. All of these would be reasonable options to give as a single agent.

Now, there was a large study—actually, it was 3 randomized phase II trials put into 1 phase III trial, called the AURELIA Trial. It was a very simple trial, open label, that randomized patients who had 1 or 2 prior therapies and had their first recurrence within the 6-month window that many people use to describe a platinum-resistant patient. It randomized them to a physician-choice chemotherapy versus that same chemotherapy plus bevacizumab. And I think the trial was well-conducted. It had 3 chemotherapy cohorts to evaluate, but as an analysis of the trial overall, what it showed was that the addition of bevacizumab to any of the chemotherapy regimens that were allowed under the physician’s discretion brought a longer progression-free survival and, in many cases, a better response rate.

So, in patients like this who I think are good candidates for that combination, any one of those chemotherapy backbones—whether it’s topotecan and the number of schedules that it was given in; liposomal and doxorubicin; or paclitaxel administered weekly—in combination with bevacizumab is a reasonable option to give patients. Sometimes, patients who have paclitaxel front-line have neuropathy and are not good candidates for paclitaxel in that setting, but that does allow us multiple other chemotherapy options to give in combination with bevacizumab.

I would summarize that, in a patient who can tolerate a drug combination such as paclitaxel and bevacizumab—especially in a patient who has ascites—this is probably one of the best or most biologically related, important therapies that we could give her.

Transcript edited for clarity.

July 2016

• A 38-year old female presented to her gynecologist with abdominal distension, abdominal pain, fullness after eating, and increased urination frequency for 2 months
  • Pelvic examination revealed a suspicious mass on the left ovary
• Laboratory findings:
  • CA-125: 785 U/ml
  • Genetic testing forBRCA1/2, negative
• CT with contrast of the pelvis, abdomen, and chest indicated widespread peritoneal lesions
• She was referred to gynecologic oncology and underwent hysterectomy, bilateral salpingo-oophorectomy, omentectomy, and tumor debulking; She had diffuse studding in the omentum and diaphragmatic surfaces
• Stage 3C ovarian cancer
• She achieved complete removal of gross residual disease (R0)
• Pathology, high-grade endometrioid adenocarcinoma, ovarian primary
• The patient was started on therapy with carboplatin and every-3-weekly paclitaxel

October 2016

• Post-treatment assessment revealed no evidence of disease

March 2017

• Patient complained of fatigue and chest pain
• Physical examination:
  • Lungs, moist rales bilaterally
  • Abdomen, shifting dullness
• Laboratory findings: CA-125: 1,052 U/ml
• CT imaging: left-sided pleural effusion and sclerotic lesions in the lung apical region, ascites, new hypodense lesions in the right lobe of the liver and enlarged retroperitoneal nodes were considered metastatic
• She was started on therapy with weekly paclitaxel and bevacizumab