New regimens show promise for management of advanced cervical cancer
Click Here to Manage Email Alerts
Treatment of advanced, recurrent and metastatic cervical cancer has come a long way in the past 15 years, and data on novel combinations and therapies provide hope for further progress, a speaker at Chemotherapy Foundation Symposium said.
“Cervix cancer continues to be not just a worldwide problem but a problem in the United States, with over 4,000 deaths [annually],” David O’Malley, MD, professor and division director of gynecologic oncology at The Ohio State University Comprehensive Cancer Center, said during a presentation. “Median age is only 49 years old, so think about the impact that this disease has on our patients with young families, many of them underresourced.”
About half of women with cervical cancer present with locally advanced disease, and 15% present with metastatic disease, O’Malley said. Moreover, as many as 40% of those with locally advanced disease experience recurrence.
The phase 3 GOG-204 trial, published in 2009, established platinum chemotherapy plus a taxane as the therapy of choice for advanced and recurrent cervical cancer, O’Malley said. A subsequent phase 3 trial, GOG-240, showed the addition of bevacizumab (Avastin, Genentech) to chemotherapy extended median OS from 13.3 months to 17 months.
Results of the phase 3 KEYNOTE-826 trial, which evaluated the PD-1 inhibitor pembrolizumab (Keytruda, Merck) added to paclitaxel and cisplatin or carboplatin, with or without bevacizumab, demonstrated “clear improvement” among patients with a PD-L1 combined positive score of 1 or greater and the intent-to-treat population, O’Malley said.
“Now, we’re going from [median OS of] about 17 months to 24 months,” he said.
Pembrolizumab and bevacizumab both have shown an “additive effect” on outcomes that should be considered when deciding which agents to use, O’Malley added.
Few options exist for women who progress on platinum doublet therapy.
In the second line or higher setting, overall response rates for PD-L1 inhibitors that have been studied extensively, including pembrolizumab, have shown consistent ORRs of about 15% in the overall population and about 18% in the PD-L1-positive population.
Combinations of anti-PD-1 and anti-CTLA-4 antibodies have generated higher ORRs, as have the bispecific antibody bintrafusp alfa (GlaxoSmithKline) and a combination of the antibody-drug conjugate tisotumab vedotin-tftv (Tivdak, Seagen) and pembrolizumab.
An international, randomized phase 2 trial is investigating the anti-PD-1 agent balstilimab (AGEN2034, Agenus) in combination with either the anti-CTLA-4 antibody zalifrelimab (AGEN1884, Agenus) or placebo in second-line cervical cancer.
In the single-arm, phase 2 innovaTV 204 trial, tisotumab vedotin-tftv showed a confirmed ORR of 24% (95% CI, 15.9-33.3) among 101 women with previously treated recurrent and/or metastatic cervical cancer. Researchers observed clinically meaningful, durable responses, and 79% of women had disease regression. Most treatment-related adverse events were grade 1 or grade 2, although O’Malley noted incidence of eye toxicity and the need for mitigation strategies.
Tisotumab vedotin-tftv, available through the FDA accelerated approval pathway, is now being studied vs. investigator’s choice of chemotherapy in a randomized phase 3 trial among women with second- or third-line recurrent cervical cancer. It also has been investigated in combination with other agents, including pembrolizumab.
Tumor-infiltrating lymphocyte (TIL) adoptive cell therapy remains a potential option, O’Malley said, having shown an ORR of 44.4% in a 2019 study.
“We hope to see lifileucel [LN-144, Iovance Biotherapeutics], the TILs product, in the next year or two,” he said.
References:
- Coleman RL, et al. Ann Oncol. 2020;doi:10.1016/annonc/annonc325.
- Colombo N, et al. N Engl J Med. 2021;doi:10.1056/NEJMoa2112435.
- Jazaeri AA, et al. J Clin Oncol. 2019;doi:10.1200/JCO.2019.37.15_suppl.2538.
- Monk BJ, et al. J Clin Oncol. 2009;doi:10.1200/JCO.2009.21.8909.
- O’Malley D. Forward progress: Management of advanced, recurrent, and metastatic cervical cancer. Presented at: 40th Annual Chemotherapy Foundation Symposium: Innovative Cancer Therapy for Tomorrow; Nov. 9-11, 2022.
- Tewari KS, et al. N Engl J Med. 2014;doi:10.1056/NEJMoa1309748.
Collapse
O’Malley D. Forward progress: Management of advanced, recurrent, and metastatic cervical cancer. Presented at: 40th Annual Chemotherapy Foundation Symposium: Innovative Cancer Therapy for Tomorrow; Nov. 9-11, 2022.
Click Here to Manage Email Alerts