New Vaccine Shows Monumental Survival Impact in Metastatic Cervical Cancer

June 2017, Vol 8, No 3

National Harbor, MD—Patients with recurrent metastatic cervical cancer surpassed all historical standards for 1-year survival when treated with an investigational immunotherapy targeting human papillomavirus (HPV) infection.

The 39 evaluable patients who received a Listeria-based vaccine—axal­imogene filolisbac (AXAL)—had a 1-year survival of 38%. In clinical trials conducted since 1995, no therapy for recurrent metastatic cervical cancer had surpassed a 1-year survival of 30%, according to a late-breaking report at the 2017 Society of Gynecologic Oncology meeting.

“Besides bevacizumab, AXAL is the only targeted agent to have been deemed active in metastatic cervical cancer, a significant result given the study population had received prior bevacizumab and it had failed,” said Charles A. Leath III, MD, MSPH, Associate Professor, Division of Gynecologic Oncology, University of Alabama at Birmingham.

“AXAL is being studied in the phase 3 setting in high-risk cervical cancer, and Advaxis [the developer] intends to initiate a global registrational phase 3 study in the metastatic setting later this year,” he said.

Although relatively uncommon in the United States, persistent or recurrent metastatic cervical cancer is a fatal condition that currently has no FDA-approved therapy. Historical survival duration with available therapies has ranged between 4 and 7 months.

Phase 2 Clinical Trial with AXAL

The GOG 227C trial of bevacizumab resulted in a median overall survival (OS) of 7.3 months and a 1-year survival of 30%.

AXAL is a live, highly attenuated L monocytogenes–targeted immunotherapy engineered to secrete HPV type 16 E7. The vaccine targets HPV-transformed cells, induces antitumor T-cell immunity, and breaks immune tolerance in the tumor microenvironment.

In the phase 2 randomized trial conducted in India, treatment with AXAL led to a 12-month survival of 32%, associated with acceptable toxicity in patients with treated or untreated persistent or recurrent metastatic cervical cancer.

“Activity was observed across all HPV types associated with cervical cancer,” said Dr Leath.

The favorable phase 2 results led to the GOG/NRG-0265 clinical trial of patients who received at least 1 previous line of systemic chemotherapy. Previous bevacizumab treatment was allowed but not required.

The trial was conducted in 2 stages. Statistical projections showed that treatment leading to a 12-month survival of 24.5% in 26 patients would permit rejection of the null hypothesis and progression to the second stage of the trial, involving an additional 24 treated patients.

The co-primary end points were 12-month survival and safety or tolerability. Dr Leath reported data for 50 treated patients, 39 of whom were evaluable, for the primary end point.

More than 50% of the patients had received bevacizumab, and 86% had previous pelvic radiation.

The study had a median OS of 6.2 months, and 38% of patients remained alive at the 12-month landmark survival assessment. Follow-up in some patients surpassed 40 months.

Dr Leath reported that 1 patient achieved a complete response with AXAL, and 15 had stable disease; 10 patients remained unevaluable.

Tissue samples available for 41 patients showed that 35 patients had HPV-positive disease. HPV-16 accounted for 16 of the 35 patients, and HPV-18 for 17 patients. Fourteen patients with HPV-16 or HPV-18 remained alive at 12 months; median OS in those patients was 17.8 months and 15.7 months, respectively.

Overall, the vaccine was well-tolerated. The most common treatment-emergent adverse events (all grades) were fatigue (52%), chills (52%), anemia (48%), nausea (32%), and fever (30%). Anemia was the most common grade 3 treatment-emergent adverse event, occurring in 5 patients.

“AXAL is an active therapy, based on the mean 12-month survival of 38% achieved in this heavily pretreated population,” said Dr Leath. “This represents the highest 12-month survival to date, including a compelling complete response of 18.5 months. The probability of this survival advantage being detected by chance versus a true treatment effect was 0.02.”

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