Elizabeth Swisher, MD, on Predicting Therapy Benefits in Ovarian Cancer

by Mark L. Fuerst

– KELIM score can now be used to look at upfront response, study showed

Tumor primary chemosensitivity testing can help determine if ovarian cancer patients need a boost along with first-line chemotherapy. In the VELIA trial, veliparib combined with carboplatin-paclitaxel, followed by maintenance (veliparib throughout) was associated with improved progression-free survival (PFS) compared with carboplatin-paclitaxel alone in patients with high-grade ovarian carcinomas.

A new study explored the prognostic value of the modeled cancer antigen (CA)-125 elimination rate constant K (KELIM), which is known to be an indicator of intrinsic tumor chemosensitivity.

In the following interview, Elizabeth M. Swisher, MD, co-leader of the Breast and Ovarian Cancer Research Program at Seattle Cancer Care Alliance and director of the Division of Gynecologic Oncology at the University of Washington Medicine, discussed the team’s findings in using KELIM scores in ovarian cancer.

What are the highlights of the study?

Swisher: KELIM measures chemosensitivity, based off velocity of decline of the CA125 tumor marker, which is an excellent tumor marker in ovarian cancer.

KELIM can give us an idea in real time of response to treatment. We found that increasing KELIM values — more favorable — were associated with higher benefit from veliparib in HR [homologous recombination]-deficient (HRD) cancer, as were decreasing — unfavorable — KELIM values in HR-proficient cancer.

The highest PFS benefit from veliparib was observed in patients with both favorable KELIM and BRCA mutation or BRCA wild-type HRD cancer, consistent with the association between PARP inhibitor efficacy and platinum sensitivity.

Were there any surprises in the data?

Swisher: Yes, surprisingly, patients who did not have BRCA mutations or HRD and also had unfavorable KELIM scores got more benefit from adding a PARP inhibitor. A unique aspect about the trial was that a PARP inhibitor was given along with chemotherapy.

It seems that PARP inhibitors potentiate the effect of chemotherapy in patients who do not otherwise have a favorable chemotherapy response. We don’t know if we can apply these data to the use of PARP inhibitors in the maintenance setting.

What other recent studies show the benefits of KELIM scores?

Swisher: Another publication using KELIM scores with bevacizumab therapy was presented at the 2022 ASCO annual meeting. In this study, patients with an unfavorable KELIM score showed a benefit from the addition of bevacizumab to chemotherapy. These are the same patients who benefit from adding velaparib.

If we put the data together from these two trials, we see that patients with a poor response to chemotherapy based on KELIM score can benefit from additional modalities — that is, KELIM score can define who needs an additional boost to chemotherapy. For those with a poor response to chemotherapy, we now have a way of identifying patients and potentially improving their treatment in real time with bevacizumab.

There are parallels between the two studies. Benefit is provided when either a PARP inhibitor or bevacizumab is combined with chemotherapy for patients with unfavorable KELIM scores. Unfortunately, veliparib is not FDA-approved and is not currently slated for further development.

How can KELIM score be used as a biomarker?

Swisher: We can now take an ongoing clinical trial with patients randomized at diagnosis, add in KELIM score, and use that as a biomarker.

KELIM score is inexpensive, available at no cost online, and can be used clinically for patients on neoadjuvant chemotherapy or for those undergoing primary debulking surgery. We can select those patients with unfavorable KELIM to add bevacizumab.

For 15 years we had no biomarker for bevacizumab use — it is exciting to finally have one.

How difficult is it to integrate KELIM assessment along with BRCA mutation status and HRD status to identify patients who would receive maximum benefit from veliparib?

Swisher: We give anyone with a BRCA mutation a PARP inhibitor. That is now standard of care. Another option is combining a PARP inhibitor for maintenance plus bevacizumab, although most patients do not need that. Patients with a lower KELIM score with BRCA mutation did get more of a boost from PARP inhibitors than those with a favorable KELIM score. Adding bevacizumab to those with lower KELIM scores might select out patients for combination with bevacizumab and PARP inhibitor, but this has not been formally tested.

We can apply KELIM scores into clinical trials to deliver precision medicine. Some patients don’t benefit from any maintenance, while others need bevacizumab, and still others a PARP inhibitor. A subset of patients may benefit from a combination of a PARP inhibitor and bevacizumab. That’s the direction we are heading.

What bottom-line message should we give to practicing oncologists?

Swisher: KELIM score is a biomarker that can now be used to look at upfront response to treatment in ovarian cancer. If a patient has an unfavorable KELIM score, consider adding in bevacizumab, if the patient is not already on it.

Potentially, we can consider clinical trials using KELIM score as a predictor for bevacizumab and PARP inhibitor therapy. It’s also a strong prognostic factor. In a clinical trial of maintenance, we could recommend therapy if a patient has a poor response based on the KELIM score. If a patient is on neoadjuvant chemotherapy, we can calculate the KELIM score and then make the decision about using bevacizumab.

Real-time measurement of chemotherapy response in the near future will be incorporated into treatment decision-making. There’s more to come on how to compare KELIM score to other pathologic response variables.

Read the study here and expert commentary about it here.