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NATIONAL HARBOR, Md. -- Treatment with a human papillomavirus (HPV)-targeting immunotherapy resulted in the highest-ever 12-month survival in patients with recurrent, metastatic cervical cancer, investigators reported here.

Of 50 evaluable patients, 19 survived to 12 months, translating into a 12-month overall survival (OS) of 38% for treatment with axalimogene filolisbac (AXAL). None of more than 20 Gynecologic Oncology Group (GOG) trials conducted since 1995 produced a 12-month survival exceeding 30% for patients with advanced cervical cancer, , of the University of Alabama at Birmingham, said at the .

"This represents the highest 12-month survival to date for patients with heavily pretreated, recurrent metastatic cervical cancer," said Leath. "From a statistical standpoint, the probability that this survival advantage occurred by chance is considered very low, associated with a P-value of 0.02."

"The results compare favorably with those seen with bevacizumab (Avastin) in GOG-227C (12-month survival of 30%), which subsequently gained regulatory approval in first-line combination with chemotherapy," he added. "This is significant given that about half of the patients in [the current trial] had received prior bevacizumab."

The 12-month survival data are provocative, said , of Massachusetts General Hospital Cancer Center, a co-investigator in the trial. The immunotherapeutic agent clearly warrants further investigation in patients with advanced disease and as potential therapy for patients earlier-stage disease, he added.

AXAL consists of live attenuated Listeria monocytogenes, engineered to secrete HPV-16 protein, fused with a truncated fragment of the hemolysin listeriolysin O. The conjugate targets HPV-transformed cells, induces antitumor T-cell immunity, and disrupts immune tolerance in the tumor microenvironment.

Leath reported findings from the GOG/NRG 0265 trial, involving patients with previously treated metastatic cervical cancer. More than half the patients had received at least two prior therapies, beyond initial curative-intent therapy.

Treatment consisted of three doses of AXAL, administered a month apart. The trial had primary endpoints of overall survival and safety/tolerability. The 38% survival at 12 months exceeded the prespecified benchmark by more than 50%.

In a subgroup of 33 patients with HPV genotyping data, treatment with AXAL led to 12-month overall survival of 44% and 41% in patients whose tumors tested positive for HPV-16 and HPV-18, respectively.

The most common treatment-related adverse events (TRAEs, all grades) were fatigue (52%), chills (52%), anemia (48%), nausea (32%), and fever (30%). The most common grade 3+ TRAE was anemia, occurring in five (10%) of evaluable patients.

More Late-Breaking Data

The GOG-0265 results were reported at a late-breaking abstract session that also included reports from two trials of maintenance therapy in ovarian cancer; a study of chemoimmunotherapy in recurrent, platinum-resistant ovarian cancer; and thromboprophylaxis in surgically debulked gynecologic cancers.

The ovarian cancer trial showed no survival benefit from the addition of the toll-like receptor 8 agonist motolimod (VTX-2337) to pegylated liposomal doxorubicin (PLD). Motolimod is a small-molecule agent that activates the immune system to induce an adaptive immune response, and preclinical studies showed the drug enhances response to anthracycline chemotherapy, said , of the University of Arizona and Arizona Oncology in Phoenix.

In an earlier , two-thirds of patients with advanced ovarian cancer had objective responses or stable disease when treated with motolimod plus PLD.

The phase II randomized GOG-3003 trial involved 297 patients with platinum-resistant ovarian cancer. They were randomized to PLD alone or with motolimod. Treatment continued until disease progression, and the primary endpoint was OS.

The results showed a median OS of 18.9 months with PLD alone versus 18.1 months with PLD plus motolimod. A comparison of investigator-assessed progression-free survival (PFS) showed a median progression-free interval of 5.2 months with PLD alone and 4.8 months with the addition of motolimod. Objective response rate did not increase with motolimod.

Investigators performed a prespecified analysis of injection-site reaction (ISR) and its association with survival. Three-fourths of patients in the motolimod arm developed ISRs. Patients with ISRs had a median OS of 19.8 months versus 13.3 months for those without, a difference not reaching statistical significance (P=0.067).

A final late-breaking report came from a randomized trial to compare the oral factor Xa inhibitor apixaban (Eliquis) and subcutaneous enoxaparin for postoperative thromboprophylaxis in women with gynecologic cancers. The trial has an accrual target of 400 patients. A prespecified safety analysis occurred after the first 120 randomized patients, reported at SGO by , of the University of Colorado in Denver.

Patients in both arms received thromboprophylaxis for 28 days. With that length of treatment, enoxaparin of deep-vein thrombosis and pulmonary embolism versus placebo. However, the low molecular weight heparin has disadvantages that include injection site pain, compliance issues, and bruising, said Guntupalli.

The safety analysis showed no major bleeding and no venous thromboembolic events in either treatment group. Adherence was 91% with apixaban and 86% with enoxaparin. The most common adverse event was arthralgia (7% with enoxaparin and 3% with apixaban, P=0.4). No adverse events occurred in either group after treatment stopped.

Patients reported significantly less pain with apixaban (P<0.001) and less difficulty using the oral drug (P=0.003).