Charles A. Leath III, MD, gynecologic oncologist at the University of Alabama at Birmingham, discusses agents under investigation in cervical cancer.

Pembrolizumab (Keytruda) is currently FDA approved for patients with advanced, PD-L1—positive cervical cancer with disease progression on or after chemotherapy. Data from the phase II KEYNOTE-158 trial served as the basis for the agent’s approval and provided a foundation with which to base additional immunotherapy studies on.

In addition to immunotherapy, PARP inhibitors are also under evaluation, and there is interest in antibody-drug conjugates that target tissue factor, says Leath. For example, in a small, single-arm phase II trial (NCT03438396), patients with previously treated, recurrent or metastatic disease will receive tisotumab vedotin (HuMax-TF-ADC). If these agents prove effective, the next step will be to determine their optimal sequence in treatment, concludes Leath.

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Dr. Leath on Agents Under Investigation in Cervical Cancer

Charles A. Leath III MD, gynecologic oncologist at the University of Alabama at Birmingham, discusses the results of the phase III GOG 240 trial in advanced cervical cancer.

The trial was conducted to answer 2 questions: whether patients with advanced cervical cancer could derive the same benefit with a non-platinum chemotherapy regimen as they would with a traditional method and whether bevacizumab (Avastin) added any benefit to chemotherapy, says Leath. Previously, bevacizumab had shown activity in women with persistent or recurrent cervical cancer in the phase II GOG 227C trial.

In the GOG 240 trial, women with metastatic, recurrent, or persistent cervical cancer were randomized to 1 of 4 arms: cisplatin and paclitaxel (Arm A), topotecan and paclitaxel (Arm B), cisplatin, paclitaxel, and bevacizumab (Arm C), or topotecan, paclitaxel, and bevacizumab (Arm D). Results showed an improvement in overall survival (OS) in Arm C and Arm D. The improvement in OS between Arm D and Arm B was not found to be statistically significant. Although the trial demonstrated improved outcomes with bevacizumab, investigators are still searching for potentially curative therapies for these patients, concludes Leath.

Charles A. Leath III MD, gynecologic oncologist at the University of Alabama at Birmingham, discusses results of the phase III GOG 240 trial in advanced cervical cancer.

Dr. Leath on the Results of the GOG 240 Trial in Advanced Cervical Cancer

Charles A. Leath, III, MD, gynecologic oncologist, The University of Alabama at Birmingham, discusses challenges with bevacizumab (Avastin) in the treatment of patients with cervical cancer.

Investigators were initially excited to see that the combination of standard chemotherapy with the antiangiogenic agent bevacizumab did improve overall survival, but this is only a temporary survival benefit, Leath says. These patients will inevitably recur, and the median survival for these patients is somewhere between 4 months and 8 months.

Bevacizumab is a very expensive drug, although cost is becoming less of an issue as most payers are accepting coverage of it, Leath adds. However, the agent carries some significant toxicity concerns. Long-term follow-up data presented by Krishnansu S. Tewari, MD, of the University of California, Irvine, show fistula rates around 15%. This is critical to note, says Leath, because fistula rates usually require surgical intervention. Therefore, bevacizumab is providing non-curative therapy with a high toxicity rate.

Charles A. Leath, III, MD, gynecologic oncologist, The University of Alabama at Birmingham, discusses challenges with bevacizumab in the treatment of patients with cervical cancer.

Dr. Leath on Challenges With Bevacizumab in Cervical Cancer

Charles A. Leath III, MD, gyn oncologist at the University of Alabama at Birmingham, discusses the glaring unmet need in cervical cancer.

A large proportion of women are diagnosed with advanced stage cervical cancer, says Leath, and some of those patients will have metastatic disease at the time of their diagnosis. For these patients, there are limited treatment options available. Management of this cancer pales in comparison to that of ovarian cancer, which almost seems to have a limitless amount of options, he adds.

With cervical cancer, treatment is limited primarily to chemotherapy with or without bevacizumab (Avastin) based on clinical trial data, Leath says. Although combination treatment with bevacizumab has been shown to prolong survival in these patients compared with chemotherapy alone, patients will recur, as this is not a curative therapy, he explains. After that recurrence, there is only 1 FDA-approved agent available: pembrolizumab (Keytruda).

Leath adds that although there are other therapies that can potentially be considered, there’s a clear unmet need in these patients in terms of findings alternative, more effective therapies.

View more from the 2019 SGO Winter Meeting 

Charles A. Leath III MD

Articles

Dr. Leath on Agents Under Investigation in Cervical Cancer

Dr. Leath on the Results of the GOG 240 Trial in Advanced Cervical Cancer

Dr. Leath on Challenges With Bevacizumab in Cervical Cancer

Dr. Leath Discusses Unmet Need in Cervical Cancer