"We’ve learned from our colleagues in breast cancer that there are opportunities to leverage this hormonal axis with combinations [including] a CDK4/6 [inhibitor]."
During the Society of Gynecologic Oncology (SGO) Annual Meeting on Women’s Cancer, a panel of experts discussed the phase 2 GOG 3026 trial (NCT03673124), which assessed ribociclib (Kisqali) plus letrozole (Femara) in recurrent low-grade serous ovarian cancer and traded insights on the trial’s findings.1
In GOG 3026, patients received treatment in a 3-weeks-on and 1-week-off manner during each 28-day cycle. The experimental regimen consisted of oral ribociclib at a dose of 600 mg daily during each 3-week period, followed by a week off treatment. Additionally, patients received continuous oral letrozole at a dose of 2.5 mg daily.
The study enrolled 51 patients, of whom 48 were treated and included in the analysis. The population had a median age of 58.5 years (range, 21-85), and most patients had undergone prior treatment, including chemotherapy (73%), hormonal therapy (27%), and immunotherapy (13%).
The overall response rate (ORR) was 23% (90% CI, 13.4%-35.1%), consisting of 11 partial responses. In patients who received 2 prior lines of chemotherapy, the ORR was higher at 26%. The median duration of response (DOR) was 19.1 months (range, 4.8-35.8), and the median time to response was 7.9 months (range, 2.0-22.3). The clinical benefit rate was 79% (n = 38; 90% CI, 67.2%-88.2%); it was 90% among those treated with 2 prior lines of chemotherapy. Median progression-free survival was found to be 19.1 months. Additionally, 64% (n = 27) of evaluable patients (n = 42) experienced reductions in target lesion size.
At the time of the presentation, 38% of patients remained on the study. The most common grade 3 or higher adverse effects (AEs) included neutrophil count decrease (44%), white blood cell decrease (8%), and anemia (4%).
COLEMAN: [Low-grade serous ovarian cancer is sometimes] confused with high-grade serous ovarian cancer, [even though] it possesses some demographic and prognostic characteristics that are different than [the high-grade disease] we usually see in the clinic. Most notably, [low-grade serous disease] comes with different expectations not only [in terms of] response to treatment but also [in terms of] prognosis, irrespective of treatment.
This has also been a disease [in which treatment] has derived some benefit from molecular interrogation. We’ve learned that the endocrine axis is important in the growth parameters for this disease, as well as other molecular characteristics, such as alterations in the RAS/RAF/MEK/MAP kinase pathway and PI3K pathway. Because of that, we’ve been able to start leveraging some interesting new therapies like this drug combination.
We [as a clinical community] have some experience using these drugs independently. We have chemotherapy, we have aromatase inhibitors, and we have other hormones. We have MEK inhibition, and we have this new idea of relating these factors to endocrine resistance. We’ve learned from our colleagues in breast cancer that there are opportunities to leverage this hormonal axis with combinations [including] a CDK4/6 [inhibitor].
ESKANDER: In ovarian cancer, we’ve moved from disease homogeneity to molecular granularity. We used to lump all these patients together and put them on clinical trials that enrolled 1500 to 2000 patients. We recognize [now] that these [disease types] are very different. [Low-grade serous ovarian cancer] is a completely different disease entity [from high-grade disease]. The molecular aberrations that inform [this entity] are distinct from those that inform high-grade disease. It is not the same disease; [it’s] at a different gradation. Thankfully, we’re now designing trials which investigate agents that have a biologic rationale for their use in low-grade serous disease because of the molecular drivers of the disease. It’s an incredibly exciting time.
LEWIN: This was the lead presentation, and it was excellent to see these findings. These patients have [a disease with] a different molecular subtype. Often these patients are very young women and, to be honest, we don’t have a lot of options for them. As such, when you see response rates on the order of the MEK inhibitors, it’s exciting to have another therapeutic target for these women. I often wonder what the sequence [of treatments] will be for these patients considering these data, but it’s nonetheless exciting to see something so tolerable and effective.
COLEMAN: Are we comfortable treating low-grade serous disease without chemotherapy nowadays?
LEWIN: Yes, for sure.
ESKANDER: Yes, absolutely. Many of us are hungry to identify a strategy. These [data] should be adjudicated in a way that helps us compare the efficacy of this regimen to others. Hopefully, we will see a continued growth of these combination strategies, investigated in such a way that we can extrapolate [the data] to the clinical space. Nonetheless, a signal like this is provocative.
COLEMAN: What is your experience with prolonged duration of treatment in this disease type?
LEWIN: Some of my best experiences with MEK inhibitors are in these particular patients. Generally, I would treat until progression or some type of unacceptable toxicity. These patients [tend to be] on therapy for a very long time. We have to become familiar with the unique adverse effects of these particular agents.
COLEMAN: Do you feel comfortable counseling patients to take a break from treatment when toxicities become more apparent?
LEWIN: Yes, I do. I haven’t had to do it much because many patients want to stay on therapy, especially when it’s working. They don’t want a treatment break. [There have been some] short breaks but, by and large, [our patients] have pretty much remained on therapy [despite apparent toxicities].