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GYN ONC: A Year In Review


Long-term follow-up analyses from Phase III SOLO-1 (olaparib maintenance treatment in 1L BRCAm ovarian cancer) and Phase III PAOLA-1 (olaparib + bevacizumab maintenance treatment in 1L HRD+ ovarian cancer) yielded positive OS data, reinforcing benefit of PARPis in these settings

Mirvetuximab soravtansine (FRα targeting ADC) was approved for the treatment of FRα-positive platinum-resistant ovarian cancer who have received 1-3 prior systemic therapies, representing the first ADC to be approved in this tumor type

Phase III RUBY-1 (dostarlimab + chemo in recurrent or primary advanced endometrial cancer) demonstrated positive topline data in both the dMMR and ITT populations, making it the first IO + chemo trial to readout in this setting

Topic 1: TNBC


Topic 1: Ovarian Cancer (OC)

SOLO-1 and PAOLA-1 data strengthen the value of 1L olaparib maintenance in BRCAm and HRD+ OC patients: Long-term results of AstraZeneca’s SOLO-1 trial show that olaparib maintenance more than doubles the 5-year disease-free survival time for BRCAm patients, suggesting the possibility of long-term remission (or even cure) for some patients. Olaparib + bevacizumab provided a clinically meaningful improvement in OS for HRD+ patients according to the PAOLA-1 trial, confirming SOC in this setting.

“SOLO-1 data are phenomenal. It’s changing the world. And even though we are still waiting for full data maturity, we are clinically convinced by PAOLA-1 data.” - Tier 1 US KOL

Clovis and GSK both restrict their 2L PARPi maintenance labels to BRCAm patients: These decisions come after the FDA reviewed final OS results from Clovis (ARIEL3) and GSK (NOVA) trials. Although PARPi improved PFS across all patients in both studies, they were associated with an OS lack of benefit (ARIEL3) and detriment (NOVA). Various KOLs emphasized disappointment in the withdrawals, noting that OS in platinum-sensitive OC and later lines should be considered an exploratory endpoint due to frequent crossover and post-progression treatment variability.

“OS interpretation was confounded by not controlling for choice, timing, or sequencing of therapies in the post-progression period, including substantial cross-over to PARPi. OS was a non-analytic endpoint in these studies, and the OS analyses were underpowered. PFS, PFS2, and TSST are sufficient for making clinical decisions and support the use of PARPi in 2L maintenance.” - Tier 1 EU KOL

The FDA grants accelerated approval of ADC ELAHERE for the treatment of FRα+ platinum-resistant OC patients who have received 1-3 prior systemic treatment regimens: Based on the single-arm Phase III SORAYA trial, ELAHERE is the first ADC to be approved in OC and the first treatment regimen to be approved specifically for platinum-resistant OC since 2014. The approval is in patients regardless of prior bevacizumab usage, likely due to preliminary ORR and DOR data that the FDA requested from the confirmatory MIRASOL trial, which included both bev-naïve and bev-pretreated patients. Immunogen has been communicating that ~35% of PROC patients will test positive for FRα (defined as ≥75% FRα+ tumor cell staining with 2+/3+ intensity). Many KOLs do not view ELAHERE's black box warning as being a major barrier to uptake.

“I am very excited about the mirvetuximab approval, and I believe a majority of FRα+ patients will get mirvetuximab in PROC, either as a monotherapy or in combination with bevacizumab. I don’t expect the black box to substantially impact its use. We’ve gotten used to managing ocular toxicities in the gyn space after the tisotumab vedotin approval in CC, and mirvetuximab has a less restrictive back box label than tisotumab.” -Tier 1 US KOL

Topic 2: Cervical Cancer (CC)

Phase III CALLA trial evaluating durvalumab + concurrent CRT in locally advanced CC does not show statistically significant PFS benefit based on an interim analysis: The study did not meet its primary endpoint of statistically significant improvement in PFS compared to CRT alone. Consistent with the PFS data, there was no significant improvement in OS, although these data are not mature. KOLs wonder about the potential role of concurrent CRT in helping or hindering IO efficacy, and RT timing, dosing, and fractioning will become important considerations in interpreting future IO trial results in LACC. Of note, physicians are cautiously optimistic about future results of the Phase III KN-A18 study, which evaluates pembrolizumab + concurrent CRT in this setting, based on key trial differences.

Cemiplimab is approved for 2L+ CC in Europe and Japan, irrespective of PD-L1 status: Based on the Phase III EMPOWER trial, cemiplimab was approved by the European Medicine Agency and Ministry of Health, Labor, and Welfare in Japan. Regeneron presented the final OS analysis at a median follow-up of 30 mos. at ESMO 2022 (ITT: 11.7 vs. 8.5 mos.; HR: 0.66). Many EU KOLs are pleased with having a new treatment option, although reimbursement policies according to biomarker status may differ across countries.

“Overtime as the KN-826 regimen is used more, the use of cemiplimab will decrease, but there will always be a subgroup of patients who are PD-L1- where we will be happy to use cemiplimab, and I say that despite the future approval of tisotumab vedotin in the EU. If you can use a CPI in CC, you should do it.” - Tier 1 US KOL

AK104 (PD-1 X CTLA-4 bispecific) is approved for 2L+ CC in China, irrespective of PD-L1 status: Based on positive results from a PII China-based trial, the PD-1 / CTLA-4 bispecific antibody was approved by the National Medicinal Products Administration earlier this year. Results from the study were presented at SGO 2022, showing an ORR of 33%, with a mPFS and mOS of 3.8 and 17.5 mos., respectively. Akesobio’s AK104 clinical development spans across all LOTs for CC, but the global registrational potential of ongoing studies remains unclear.

Topic 3: Endometrial Cancer (EC)

In a planned interim analysis, the Phase III RUBY-1 trial meets one of its primary endpoints, PFS, in the pre-specified dMMR/MSI-H subgroup and ITT populations: RUBY-1 evaluates dostarlimab and chemo followed by dostarlimab maintenance. GSK noted that a “clinically relevant benefit” was also observed in the pMMR/MSS subgroup. Although OS data were immature at the time of analysis, GSK noted that a favorable trend was observed across ITT as well as dMMR/MSI-H and pMMR/MSS subgroups. We eagerly anticipate the full data presentation as we think about the future biomarker segmentation of 1L EC based on upcoming IO monotherapy, IO + chemo, and IO + TKI trials.

“We all think IO + chemo will work well in dMMR patients, and looking towards the IO monotherapy trials, maybe we won’t even need chemo at all” - Tier 1 US KOL

Phase III KN-775 continues to demonstrate clinically meaningful improvement in OS, PFS, and ORR of lenvatinib and pembrolizumab vs. chemo, across pMMR and all-comer advanced EC: OS KM curves of the two arms separated early and remained separated, despite some patients in the chemo arm receiving subsequent lenvatinib pus pembrolizumab. Results continue to support the use of the IO + TKI combination as a standard therapy in pMMR advanced EC patients who have received prior platinum therapy.


Axiom Catalyst hosted an episode on the latest gyn onc developments in January 2023, where we recapped the impact of ADC approvals in CC and OC, new PARPi data in OC, and exciting IO results in 1L EC.

The Latest in Gynecologic Oncology Spotify Link Available Here


For Details on Axiom’s Capabilities in Gynecologic Oncology, Contact:

Hafiz Sikder –

Joel Tamayo –

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