Second- and Third-Line Treatment Options for Ovarian Cancer

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Erin Crane, MD, reviews second- and third-line treatment options and the impact of platinum sensitivity on treatment selection.

Erin Crane, MD: When we are talking about second- and third-line options for this patient, determining what to use in the second-line setting depends on platinum sensitivity. For the majority of patients who are platinum-sensitive, we would combine a platinum-based agent with another cytotoxic treatment. As it was in this patient’s case, we would typically rechallenge the patient with paclitaxel. We could use gemcitabine, which of course can be combined with cisplatin or carboplatin. In this patient’s case, she received cisplatin. We often use liposomal doxorubicin, or Doxil. Progression-free survival does not really differ between those regimens.

For second-line therapy, the decision to rechallenge a patient with a platinum-based agent depends on whether they are sensitive to platinum. For patients who are platinum-sensitive, we will combine a platinum with 1 of 3 agents, like liposomal doxorubicin, gemcitabine, or paclitaxel. Both retrospective and prospective studies have shown that there is not a significant difference in progression-free survival: about 8 to 10 months in the recurrent setting and for those with platinum sensitivity. What we do take into consideration, of course, is the toxicity. If someone has had paclitaxel before, for example, and they had significant neuropathy, then that may be something you do not want to use again for that patient. The nice thing about liposomal doxorubicin and gemcitabine is that they do not cause hair loss, which is important to women.

Choosing the next treatment regimen depends on platinum sensitivity, the [adverse] effects of the drugs, and the toxicities the patient has experienced before. For third-line therapy, if the patients are still platinum-sensitive like this patient was, then again, we would use a platinum-based agent and combine it with one of the other drugs that the patient has not received in the past. However, many patients, at that point have developed a platinum-resistant disease, which of course is defined as disease recurrence within 6 months of the completion of the last platinum-containing regimen. In that case, we tend not to use combination therapy because we know that it adds to the toxicity and unfortunately does not add much benefit in terms of efficacy.

Again, we choose single agents like liposomal doxorubicin; sometimes we use topotecan. Weekly Taxol [paclitaxel] is also a popular one. At that point, if the patient has not already received bevacizumab, then we would use bevacizumab; we know that can add benefit based on the results of the AURELIA trial. It may provide a few months of progression-free survival, which in the platinum-resistant setting is clinically significant for patients.

This transcript was edited for clarity.

Case: A 63-Year-Old Woman With Recurrent Ovarian Cancer

Initial Presentation

  • A 63-year-old female presented with early satiety and abdominal discomfort
  • PMH: unremarkable, postmenopausal; no known family history of cancer
  • PE: left lower quadrant tenderness on palpation
  • ECOG PS 1

Clinical work-up

  • Pelvic exam with transvaginal ultrasound showed a left ovarian mass
  • Transvaginal U/S showed a left ovarian mass
  • Chest/abdomen/pelvis CT with contrast confirmed a left adnexal 4.4-cm mass with paraaortic lymph node involvement and ascites
  • Paracentesis (1000 cc) cytology confirmed high-grade epithelial ovarian cancer
  • Germline molecular testing: HRD+, BRCA1/2-
  • CA-125, 370 U/mL
  • Diagnosis: Stage III, high-grade epithelial ovarian cancer

Treatment

  • Patient underwent TAH/BSO, lymph node dissection, with optimal debulking; R0
    • Paclitaxel/carboplatin q3 weeks for 6 cycles; CA-125 decreased; PR
  • At 7-month post treatment follow-up imaging showed progression of disease
    • Paclitaxel/carboplatin + bevacizumab was initiated q3 weeks for 6 cycles
  • At 14-months CA-125 had increased
    • Cisplatin/gemcitabine was initiated, PR
    • Initiated niraparib maintenance

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