David O'Malley, MD, Ohio State University James Comprehensive Cancer Center, discusses results from a subgroup analysis of the ARIEL4 trial, comparing rucaparib vs chemotherapy among platinum-sensitive patients with BRCA-mutated, advanced, relapsed ovarian cancer.

This analysis was presented by Amit Oza, MD, Princess Margaret Cancer Centre, University Health Network, Toronto, ON, Canada, at the virtual 2021 ASCO Annual Meeting.

Transcript

Hello, my name is Dr David O'Malley. I'm at the Ohio State University in the James Comprehensive Cancer Center, where I have the honor to lead the division of gynecological oncology.

I'd like to take this opportunity to discuss subgroup analysis of rucaparib versus chemotherapy as treatment for BRCA‑mutated, advanced, relapsed ovarian cancer, the effect of platinum sensitivity in the randomized phase 3 study, ARIEL4, presented by Dr. Amit Oza at this year's ASCO.

To remind everybody, this trial enrolled patients with BRCA1/2 mutations, either germline or somatic mutations. Patients were allowed to have unlimited prior therapies and were classified in the platinum‑resistant ovarian cancer, defined as recurring within 1 to 6 months from last platinum, partially platinum‑sensitive, 6 to 12 months, or fully platinum‑sensitive beyond 12 months.

Rucaparib was compared to weekly paclitaxel dose of 60 to 80 milligrams weekly. To clarify, the chemotherapy arm in those that were platinum‑resistant or partially platinum‑sensitive, received weekly paclitaxel. Those that are considered fully platinum‑sensitive either received cisplatin, carboplatin, or a platinum doublet.

When we look at the results of the original report, we saw a hazard ratio of 0.64, or 36% improvement in the intent to treat with a median progression‑free survival of 7.4 months in the rucaparib arm versus 5.7 months in the chemotherapy arm. This was very important, and that was the first trial that compared patients who had received platinum or a platinum doublet.

Now, what wasn't presented originally was the sub‑analyses that looked at those patients with platinum‑resistant, partially platinum‑sensitive, and fully platinum‑sensitive, and that was the goal of this year's presentation.

To remind people, when we look at the number of patients who had previously number of prior therapies, about half the patients had more than three prior therapies, some patients having 6 to 9 prior therapies. We look at the subpopulations in the subgroups of platinum‑resistant patients, we see at least equivalent outcomes compared to chemotherapy.

Let's talk about each one of those groups a little bit more. In the platinum‑resistant subgroup, the hazard ratio is 0.78. It's important to note that these 95% confidence intervals crossed one. The median progression‑free survival is 6.4 months in the rucaparib arm and 5.7 months in the chemotherapy arm.

In the partially platinum‑sensitive group—and remembering in the partially platinum‑sensitive, weekly paclitaxel was the set of toxic arm—we have clear benefit of rucaparib with a hazard ratio of 0.4 when compared against weekly paclitaxel, median progression‑free survival of 8 versus 5.5.

In the fully platinum‑sensitive, now we're comparing rucaparib to platinum‑based chemotherapy, most of which received platinum doublet, we see an advantage, a non‑statistically significant advantage, important to know, with a hazard ratio of 0.69. Once again, 95% confidence intervals are crossing one.

When we look at the median progression‑free survivals, we see rucaparib having 12.9 months and chemotherapy having 9.6. One of the most interesting findings within these curves is the tail with about 20% of patients being progression‑free beyond two years. When they looked at the subgroups of the efficacy populations, we see, again, these benefits persisting across all subgroups.

Another interesting finding is they reported the response rates. We look at the response rates, we see that rucaparib versus chemotherapy in the platinum‑resistant group had a 23% response rate for rucaparib with about 27% response rate for chemotherapy.

In the partially platinum‑sensitive, we had a 53% response rate for rucaparib and a 20% response rate for chemotherapy. In a fully platinum‑sensitive, we have a 64% response rate versus 57% response rate in rucaparib vs chemotherapy.

What does this mean? We have very clearly that patients with BRCA mutations, no matter when it is diagnosed, if it's a somatic or germline, they will benefit from a PARP inhibitor. Is it a reasonable option to sequence a PARP inhibitor prior to platinum‑based therapy in a patient who is, fully platinum‑sensitive? I think it's reasonable.

We actually see patients whose disease is controlled for a long term. We all have those patients within our practices who have recurrent disease who were found to be BRCA‑positive the PARP inhibitors kept their disease at bay for many years.

Even in the patient population who are platinum‑resistant, which previous data would call into question using a PARP inhibitor, when the patients have a BRCA mutation, that a PARP inhibitor is a very reasonable treatment option. A treatment option.

Those that are partially platinum‑sensitive, though that was the greatest benefit, what we can say is that a PARP inhibitor in a BRCA‑positive patient, germline or somatic, is a very reasonable option.   

Oza AM, Lisyanskaya AS, Fedenko AA, et al. Subgroup analysis of rucaparib versus chemotherapy as treatment for BRCA-mutated, advanced, relapsed ovarian carcinoma: Effect of platinum sensitivity in the randomized, phase 3 study ARIEL4. Presented at: the 2021 ASCO Annual Meeting; June 4-8, 2021; virtual. Abstract 5517.