Study Shows Zejula's Benefit in Treating Ovarian Cancer

[joann86]

Below is a follow-up article about Zejula, the new drug being used in certain types of ovarian cancer treatment. Below are some preliminary results- looks promising.

"Superior progression-free survival (PFS) was seen in patients with ovarian cancer who previously had a partial response (PR) to platinum-based therapy when they took Zejula (niraparib). This response was seen in patients with or without germline BRCA mutations, according to data from the ENGOT-OV16/NOVA trial presented at the 2017 ASCO Annual Meeting.

Investigators set out to explore the effect of the PARP inhibitor Zejula on PFS in patients with recurrent ovarian cancer who were in response (either complete response [CR] or PR) to their most recent platinum-based therapy after a minimum of our cycles in ENGOT-OV16/NOVA, a phase 3 multicenter, randomized, double-blind, placebo-controlled study.

At the time of unblinding, 45 percent in the Zejula group who were positive for mutant BRCA achieved PFS, compared with 72 percent of patients in the placebo group. In the non-BRCA mutant cohort, 56 percent of patients had PFS versus 80 percent in the placebo group.

'“We had half of the population in both groups who had only partial remission and wanted to know how they were doing. We tried to show the patients who were in partial remission have the same PFS as the whole group,” lead investigator Mansoor Raza Mirza, M.D., chief oncologist in the Department of Oncology in Rigshospitalet, Copenhagen University Hospital, Denmark, and medical director of the Nordic Society of Gynecologic Oncology-Clinical Trial Unit, said in an interview with CURE. “PFS is actually better in the non-germline BRCA group because patients with active disease in the placebo group are progressing much faster so you see a better split as a hazard ratio [HR].”

'

Roughly half of the total study population (272 patients) responded to had a to their last platinum-based therapy. These patients were segregated by BRCA mutation status and assigned to either daily 300 mg Zejula daily or placebo until disease progression or unacceptable toxicity. In the germline mutant BRCA cohort, 67 out of 138 patients in the Zejula arm (49 percent) and 32 out of 65 patients in the placebo arm (48 percent) entered the trial with a PR. In the non-mutant germline BRCA cohort, 117 out of 234 patients in the Zejula arm (50 percent) and 56 out of 116 in the placebo arm (48 percent) entered the trial with a PR.

Randomization was further stratified based on time to progression after completion of the penultimate platinum regimen, the use of Avastin (bevacizumab), and the best response (CR or PR) during the final platinum regimen. Each patient had received at least two prior courses of platinum-based chemotherapy but no prior treatment with a PARP inhibitor.

Disease assessment included imaging performed at baseline every eight weeks through cycle 14, and then every 12 weeks until treatment was discontinued. Disease progression was determined via central review using RECIST v1.1 criteria or clinical assessment. Increased levels of CA-125 alone were not considered to indicate progression.

Researchers determined that the safety profile of Zejula-treated patients with a PR was similar to that of the overall study population. The concluded that, overall, treatment with Zejula provided a statistically significant benefit in patients with a PR, with a treatment effect similar to that observed in the overall study population in both the germline BRCA mutant and non-mutant cohorts.

In March 2017, the FDA approved Zejula for the maintenance treatment of adult patients with recurrent epithelial ovarian, fallopian tube, or primary peritoneal cancer who are in complete or partial response to platinum-based chemotherapy.

The approval was based on the overall findings from the ENGOT-OV16/NOVA trial, in which Zejula reduced the risk of progression or death by 74 percent compared with placebo for patients with germline BRCA-positive platinum-sensitive, recurrent ovarian cancer.

The median PFS with maintenance Zejula was 21 months compared with 5.5 months for placebo in patients with germline BRCA mutations. These findings remained consistent across subgroups of patients, including those without BRCA mutations."

Full article here: bit.ly/2tlkcjB

[miyoshi]

After chemo and possible surgery, my docs at UCLA are planning to put me on Niraparib (Zejula) or Rucaparib (I'm non-BRCA1 or 2), There are other PARP inhibitors coming down the line. Info on rucaparib:

oncotherapynetwork.com/gyne...

[joann86 in reply to miyoshi]

Hey miyoshi , thanks for sharing. Sending good vibes your way and hoping that this treatment works.

[miyoshi in reply to joann86]

Thanks so much.

[Mousse]

Thank you for sharing. In April 2016 I had major ovarian cancer surgery followed by an 18 week course of chemo (Taxol, Carboplatin, and Avastin.) After a brief break my Dr. put me on Avastin maintenance, one infusion every 3 weeks. After 9 infusions I developed joint pains that we believe were brought on by Avastin. About a month ago, I had emergency surgery for an incarcerated hernia. My surgeon and gynecological oncologist partnered and had samples if the hernia and nearby fluids sent to the lab for assessment. The detailed labs came back yesterday. There was no evidence of cancer cells in the hernia but cells were detected in the fluids near my bowel. We were of course shocked because my CA 125 tests were running in the 25 range post chemo. While I am waiting for my recent surgery to heal, I am looking at PARP therapies. We will not start a therapy until I have another PET scan. I trust my Gyn/Onc team at Palo Alto Medical group. My Dr. did suggest I seek a second opinion at Stanford where there are some immunology trials in place. Even though my hernia surgery was painful, it it hadn't been for that surgery, we would not have detected the cancer cells until there was tumor growth or the development of other symptoms. I am interested in hearing more from women or are currently on PARP maintenance. The three drugs we discussed are niraparib, olaparib, and rucaparib.

[joann86]

Hi Mousse , thanks for sharing. Sounds like it's been quite the journey; sending you lots of good vibes and hoping that one of these treatment options will work for you. Please keep us updated whenever you get the chance.

[Mousse in reply to joann86]

I am 6 weeks into my Rubraca treatment. So far the side effects are minimal - a bit of nausea mitigated by compazine. Since undergoing chemo last year my CA - 125 has been <35. Last week it dropped to 17.2.

[miyoshi]

There have been recent articles about the cost of Zejula and that Medicare has no obligation to cover it: cancernetwork.com/ovarian-c...

"Costs associated with PARP inhibitors were 7.1 to 8.3 times more than platinum combinations... In conclusion, “While the data on the PARP inhibitors is promising, the unfortunate nature of new therapies is their inherent associated high costs reflecting the high costs of development. The primary expense of these therapies lie in the high cost of the drug, rather than the complications associated with their use.”

I am still finishing up with 2 more rounds of chemo, so haven't addressed the on-going cost of this drug yet. This makes the threats to the ACA even more distressing.