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Gyn Conferences 2022

CME

Expert Analyses of Key Clinical Developments and Updates Across Gynecologic Malignancies

Physicians: Maximum of 1.00 AMA PRA Category 1 Credit™

Released: January 23, 2023

Expiration: January 22, 2024

CME/CE Information

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Use of PARP Inhibitors in Patients With Ovarian Cancer

David Scott Miller, MD, FACOG, FACS:
Our ability to identify markers of treatment response in ovarian cancer is still developing. HRD may be the best marker for response to PARP inhibitors currently, but there probably are better markers yet to be defined. However, we know from case series that once patients have progressed on a PARP inhibitor, they are unlikely to respond as well to subsequent platinum-based CT.1 That is why we need to talk to patients with homologous recombination proficient (HRP) disease about the potential benefit of a PARP inhibitor, such as niraparib, for which we have the strongest evidence in patients with or without HRD as a biomarker.2

Angeles Alvarez Secord, MD, MHSc:
The PRIMA trial compared niraparib vs placebo in patients with newly diagnosed advanced ovarian cancer who had a CR or PR to first-line platinum-based CT.2,3 PRIMA recruited a patient population with a poor prognosis, and data were reported in patient subgroups who demonstrated the best response. Patients whose tumors were HRD achieved the best response from niraparib, but also a benefit was seen in those who had HRP disease. Of note, patients with tumors responsive to platinum-based CT also are likely to benefit from a PARP inhibitor.

Individualized-Dose Niraparib vs Placebo Maintenance in Newly Diagnosed Advanced OC (PRIME): Study Design

Angeles Alvarez Secord, MD, MHSc:
At SGO 2022, Li and colleagues reported data from the phase III PRIME study evaluating maintenance therapy with individualized niraparib dose of either 200 mg QD or 300 mg QD if body weight ≥77 kg and platelet count ≥150,000/mL vs placebo in patients with stage III/IV ovarian cancer with CR or PR to platinum-based CT. The primary endpoint was PFS by blinded independent central review (BICR) in the intention-to-treat (ITT) population.

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PRIME: PFS by BICR in ITT (Primary Endpoint)

Angeles Alvarez Secord, MD, MHSc:
The PRIME study supports the overall findings of the PRIMA trial regarding the efficacy of niraparib in platinum-sensitive ovarian cancer.4 The PFS was significantly improved in the ITT population with niraparib maintenance compared with placebo (HR: 0.45; P <.001). Benefit was seen across several BRCA mutation and HRD status subgroups, with HRs ranging from 0.40-0.58. That being said, PRIME was conducted in China, and I wonder how generalizable those results are to my patient population in the United States. We know there are pharmacogenomic differences and probably some differences in how disease is managed after receiving treatment with niraparib.

 

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PRIME: PFS by HRD Subgroups

Angeles Alvarez Secord, MD, MHSc:
HRD is not a perfect biomarker, and we need to identify a better biomarker to direct treatment. In lieu of that, HRD is the best marker we have to identify patients who are most likely to benefit from PARP inhibitors. My preference for patients with HRP disease is to offer them a clinical trial that can provide access to a novel therapy. There are some data that show little benefit from PARP inhibitors for HRP disease based on tumor biology and progressive disease—one of the ARIEL studies first showed that, and my clinical experience supports it.5

Phase III of Selinexor vs Placebo Maintenance in Recurrent Endometrial Cancer (SIENDO): Study Design

David Scott Miller, MD, FACOG, FACS:
At SGO 2022, Vergote and colleagues presented data from the phase III ENGOT-EN5/GOG-3055/SIENDO trial evaluating maintenance treatment with selinexor in patients with stage IV or first-relapse endometrial cancer who had a PR or CR to 12 or more weeks of first-line therapy with taxane-carboplatin. Patients received either weekly selinexor at 80 mg or placebo. If BMI was <20 kg/m2, the dose could be lowered to 60 mg weekly. The primary endpoint of the trial is PFS by investigator.6

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SIENDO: PFS and QoL With Selinexor vs Placebo Maintenance in Recurrent Endometrial Cancer

David Scott Miller, MD, FACOG, FACS:
The investigator-assessed PFS was significantly improved with maintenance selinexor when compared with placebo (median PFS: 5.7 vs 3.8; HR: 0.705; one-sided P = .024). With a median follow-up of 10.2 months, the PFS probability at 12 months was 35.3% vs 25.8% in favor of the selinexor arm compared with the placebo arm.

Patients with cancer will endure much, but one of the things we hope to improve with treatment is their quality of life (QoL), which I also refer to as “doctor-free time.” In that sense, weekly dosing is not as good as dosing every 3 weeks or every 6 weeks, but it is better than dosing every day.

Angeles Alvarez Secord, MD, MHSc:
I agree. And selinexor is available as oral tablets administration. 

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Immunotherapy in Advanced Cervical Cancer

Angeles Alvarez Secord, MD, MHSc:
We have seen some interesting data on the use of immuno-oncology therapy in recurrent/advanced cervical cancer, which has encouraged further development into the frontline setting.

The ongoing KEYNOTE-A18/GOG 3047 trial is a phase III study of chemoradiotherapy with or without pembrolizumab in patients with locally advanced cervical cancer (NCT04221945). This trial is still recruiting participants, but we are very much looking forward to seeing the results for this study. Another key phase III trial, the CALLA trial, is evaluating the addition of durvalumab or placebo to chemoradiotherapy in women with locally advanced cervical cancer (NCT03830866). A company press release earlier in the year reported that durvalumab did not significantly improve PFS compared with placebo in that study. That was a surprising result, in my opinion. Data for CALLA were later presented at the 2022 IGCS annual meeting, and Drs Banerjee and Mirza will cover that conference later in this module.

David Scott Miller, MD, FACOG, FACS:
I think we have assumed that essentially all the PD-1/PD-L1 inhibitors are the same, but that early press release from CALLA, and later results at IGCS, reminded us that this is not necessarily true. Many people think that radiation therapy and an immuno-oncology agent ought to be synergistic, so I too am looking forward to seeing data from the KEYNOTE-A18/GOG 3047 trial.

Tisotumab Vedotin in Cervical Cancer: Background

David Scott Miller, MD, FACOG, FACS:
The tissue factor-targeted antibody–drug conjugate (ADC) tisotumab vedotin has become our go-to therapy in second-line treatment for cervical cancer based on data from the phase II innovaTV 204 study that evaluated tisotumab vedotin in previously treated recurrent or metastatic cervical cancer.7

In September 2021, tisotumab vedotin received FDA accelerated approval as a second-line treatment for patients with recurrent or metastatic cervical cancer and disease progression on or after CT regardless of a biomarker.8 Tisotumab vedotin also is the second-line therapy of choice for patients with progression on pembrolizumab plus platinum-based CT in frontline treatment or if their tumor lacks an actionable biomarker. In the innovaTV 204 study of tisotumab vedotin, the ORR was 24%, median duration of response was approximately 8 months (95% CI: 4.2-not reached), and OS was 12 months.

Tisotumab Vedotin Adverse Events of Special Interest: Ocular Toxicity, Bleeding, Neuropathy

David Scott Miller, MD, FACOG, FACS:
Tisotumab vedotin is associated with ocular adverse events (AEs), and patients receiving this therapy require a visual examination before every dose and as clinically indicated. I work in a large county hospital, and having to involve other consultants to manage my patients, particularly ophthalmologists, is a challenge given that these are not particularly complex examinations.

As we learn more about these various ocular toxicities with tisotumab vedotin, I hope we will be able to make using these treatments a little less labor intensive. We have done that with immune-related toxicities. Now, we have to step up our expertise in relation to ocular toxicities.

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