Overall survival in recurrent, metastatic cervical cancer was substantially extended with a Listeria-based immunotherapy approach that targets the human papillomavirus (HPV), investigators reported at the Society of Gynecologic Oncology Annual Meeting.¹

This represents the highest 12-month survival to date for patients with heavily pretreated, recurrent metastatic cervical cancer.

— Charles A. Leath III, MD, MSPH

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Of 50 evaluable patients, 19 were alive at 12 months, which translated into a 12-month overall survival rate of 38% for treatment with axalimogene filolisbac. Among 20 recent trials by the Gynecologic Oncology Group (GOG), this is the first to produce a survival rate higher than 30% at 12 months for patients with advanced cervical cancer, said Charles A. Leath III, MD, MSPH, of the University of Alabama at Birmingham. The study’s first author was Warner Hugh, MD, also of the University of Alabama. The study was conducted at a dozen U.S. cancer centers.

The investigators noted that overall survival was more than a 50% improvement over the expected survival in this population of patients. “This represents the highest 12-month survival to date for patients with heavily pretreated, recurrent metastatic cervical cancer,” Dr. Leath noted.

Dr. Leath said the results are comparable to those achieved with bevacizumab (Avastin) in GOG-227C. The 12-month survival rate of 30% in that study led to the drug’s regulatory approval in the first-line setting in combination with chemotherapy. “This is significant, given that about half of the patients in the current trial had received prior bevacizumab.”

Axalimogene filolisbac consists of live attenuated Listeria monocytogenes, engineered to secrete HPV16 protein, fused with a truncated fragment of the hemolysin listeriolysin O. The conjugate targets HPV-transformed cells, induces antitumor T-cell immunity, and hinders immune tolerance in the tumor microenvironment.

Key Findings

The findings came from the phase II GOG-0265 trial of patients with previously treated metastatic cervical cancer. More than half the patients had received at least two prior therapies, beyond initial curative-intent treatment. Patients received monotherapy with three doses of axalimogene filolisbac, administered a month apart.

The primary endpoint, overall survival, was 38% at 12 months, which exceeded the prespecified benchmark by more than 50%. By subgroups, 12-month survival was 44% among patients harboring the HPV16 subtype and 41% for those with HPV18.

The most common treatment-related adverse events of all grades were fatigue (52%), chills (52%), anemia (48%), nausea (32%), and fever (30%). The most common grade 3/4 event was anemia, which occurred in five (10%) evaluable patients.

“The big picture is we now have a treatment that has made it all the way through a phase II trial that appears to have activity for treating recurrent cervical cancer,” Dr. Leath commented.

Axalimogene filolisbac is also being evaluated in two other HPV-associated cancers: head and neck and anal cancers. The U.S. Food and Drug Administration has granted axalimogene filolisbac Orphan Drug designation in each of these three clinical settings, as well as a Special Protocol Assessment for the phase III AIM2CERV trial in cervical cancer, and Fast Track designation. ■

Disclosure: Dr. Leath reported no potential conflicts of interest.

Reference

1. Hugh W, Brady WE, Dizon DS, et al: A prospective phase II trial of the Listeria-based human papillomavirus immunotherapy axalimogene filolisbac in second- and third-line metastatic cervical cancer: An NRG oncology group trial. 2017 Society of Gynecologic Oncology Annual Meeting. Abstract LBA3. Presented March 14, 2017.