Upfront Options Continue to Expand in Advanced Ovarian Cancer

Trung Nguyen, DO, MBA

Trung Nguyen, DO, MBA

Several trials have compared the use of neoadjuvant chemotherapy with primary debulking surgery in patients with newly diagnosed advanced ovarian cancer, and though the jury is still out, Trung Nguyen, DO, MBA, explained that the field continues to evolve as novel therapies such as angiogenesis inhibitors, PARP inhibitors, and immunotherapy enter the landscape.

“We are in an era of having different available options in terms of treatment. We're starting to realize that the genetic heterogeneity of ovarian cancer plays a big role in how we treat the patient and how the patient responds,” said Nguyen. “There won't be a one-size-fits-all approach. All of our patients will have to be treated with an individualized approach, both from a survival perspective and the patient’s goals of care.”

For patients who harbor BRCA mutations, olaparib (Lynparza) may become another option for physicians to choose from following the FDA’s decision to grant a priority review designation to a supplemental drug application (sNDA) for the PARP inhibitor as frontline maintenance treatment for patients with newly diagnosed, BRCA-positive advanced ovarian cancer following a complete or partial response to standard frontline platinum-based chemotherapy.¹

Niraparib (Zejula) is also being investigated as an alternative frontline maintenance therapy in this patient population in the ongoing phase III PRIMA trial (NCT02655016).

OncLive: What is at the forefront of discussion in advanced ovarian cancer?

In an interview during the 2018 OncLive^® State of the Science Summit™ on Ovarian Cancer and Soft Tissue Sarcoma, Nguyen, clinical assistant professor, Obstetrics and Gynecology, Gynecologic Oncology, Stanford Medicine, discussed the evolving options for the treatment of patients with newly diagnosed advanced ovarian cancer.Nguyen: In my presentation, I discussed a topic that has generated a lot of spirited debate among gynecologic oncologists. Do we choose neoadjuvant chemotherapy or primary debulking surgery in a patient who presents with advanced ovarian cancer? Over the last decade, we have seen well-designed randomized trials. We now have 4 trials that are addressing this very question.

The first 2 trials—–EORTC 55971 and CHORUS––have been very well quoted in the literature and heavily discussed. Some have criticized the low rate of optimal debulking as well as the rate reported. Survival tends to be a little bit lower than what is reported in the United States. The subsequent trials––JGOG 0602 and SCORPION––acknowledged these issues and incorporated some of [those concerns] into their trial designs. [This was especially true of the] SCORPION trial, which triaged patients with laparoscopy. To this day, that is how we select patients for primary debulking versus neoadjuvant chemotherapy.

Are there any ongoing trials addressing the question of primary debulking surgery versus neoadjuvant chemotherapy?

What is the prevalence of neoadjuvant chemotherapy?

What else is being explored in this setting?

Neither of these trials showed the superiority of neoadjuvant chemotherapy. However, they did show that there are increasing rates of perioperative complications with primary debulking surgery. The JGOG trial did not show noninferiority. We'll have to wait for the data; the jury is still out [based on the data presented] at the 2018 ASCO Annual Meeting.The TRUST trial is comparing the use of primary debulking surgery with neoadjuvant chemotherapy. The surgeons in the trial have to have records of having handled this type of surgery and incorporate diagnostic thoracotomy in patients with pleural effusions that are greater than 500 cubic cm. It's a great trial design and it will be interesting to see the results.It's varied; it depends on the institution. I showed data from an observational study in 2016 that pulled from 6 National Comprehensive Cancer Network sites. The trend will probably go up to about 50% to 60%, which is about the rate of neoadjuvant chemotherapy that we see at Stanford Medicine.Maintenance therapy is also a concept that we have been looking at. Chemotherapy, radiation, and vaccines have all been explored as options for consolidation or maintenance therapy. Unfortunately, they didn't show an improvement in survival.

PARP inhibitors have demonstrated activity in the maintenance setting. Could these agents possess potential as a frontline therapy?

Now, we have angiogenesis inhibitors, PARP inhibitors, checkpoint inhibitors, and immunotherapy. There are options following frontline treatment with carboplatin and paclitaxel. It's encouraging to see the overwhelmingly positive results of the SOLO-1 trial. It’s quite exciting to see a disease-free survival in 50% of patients with BRCA mutations who received maintenance olaparib versus 11% in those who received placebo. It’s exciting to see that we now have another option to offer patients after upfront chemotherapy. Now, we've started to open the door in terms of incorporating genetic mutations into selecting frontline treatment for patients.It's interesting to think about how mechanisms of PARP inhibitors work. There's evidence to support that tumor cells undergo DNA damage with carboplatin and taxanes. Whether we want to capitalize on how PARP inhibitors work [by adding them to] this backbone remains to be seen. It's a very intriguing idea. [We’ve also seen their activity] in the recurrent setting. It's going to be very intriguing to see where we start using PARP inhibitors. At least we have options.

Moore K, Colombo N, Scambia G, et al. Olaparib maintenance therapy following first-line platinum-based chemotherapy in patients with FIGO stage III—IV ovarian cancer (OC) with a BRCA1/2 mutation (BRCAm): phase III SOLO1 trial. In: Proceedings from the 2018 ESMO Congress; October 19-23, 2018; Munich, Germany. Abstract LBA7_PR.