Immunotherapy AXAL Tops Survival Mark in Cervical Cancer

Charles A. Leath III, MD

An immunotherapy targeting human papillomavirus (HPV)-infected cells led to an unprecedented 1-year survival rate in patients with recurrent, metastatic cervical cancer, according to a phase II study reported at the 2017 Society of Gynecology Oncology Annual Meeting.

The 50 patients treated with axalimogene filolisbac (AXAL) had a 12-month overall survival (OS) of 38%. The result is at least comparable to, and possibly better than, the best outcomes reported with currently available therapies.

“This represents a 52% improvement versus the logistic model-predicted milestone survival rate of 24.5%,” said Charles A. Leath III, MD, a gynecologic oncologist at the University of Alabama at Birmingham. “This represents the highest 12-month survival to date in this patient population.”

The results compared favorably with those of a previous Gynecologic Oncology Group (GOG) trial of bevacizumab (30% 1-year survival), which subsequently received FDA approval for combination treatment of advanced cervical cancer. About half the patients in the current trial had received prior bevacizumab, Leath noted.

AXAL immunotherapy consists of live attenuated Listeria monocytogenes, bioengineered to secret HPV-16 E7 protein, fused with a truncated fragment of the hemolysin listeriolysin O. The immunotherapeutic agent targets HPV-transformed cells, induces antitumor T-cell immunity, and breaks immune tolerance in the tumor microenvironment.

In an earlier phase II trial, AXAL plus or minus cisplatin, led to a 12-month survival of 32% in patients with previously treated cervical cancer.

Leath reported findings from the phase II GOG/NRG 0265 trial involving patients with recurrent, metastatic cervical cancer, a group of patients for which no approved second-line therapy exists. Patients with recurrent metastatic cervical cancer have an OS of 4 to 7 months.

“From 1998 to 2015, the GOG conducted more than 20 phase II studies in persistent or recurrent metastatic cervical cancer, and not 1 of them had a 12-month OS exceeding 30%,” said Leath. “The GOG 227C trial of bevacizumab had a median overall survival of 73 months and a 12-month OS of 30%.”

Investigators in GOG/NRG 0265 enrolled 63 patients in 2 stages. All of the patients had received at least 1 prior line of systemic therapy for recurrent/persistent metastatic cervical cancer, beyond primary curative treatment.

The first stage of the trial included 27 patients. If AXAL led to a 15% absolute improvement in the benchmark 1-year survival of 20% (later refined to 24.5%), the trial would proceed to the second stage. After that goal was met, investigators enrolled an additional 36 patients. The coprimary endpoints were 12-month OS and safety/tolerability of AXAL.

Leath reported findings for 50 evaluable patients, who had a median age of 46 (range, 29-70). A majority of the patients (26/50) had received 2 or more prior lines of therapy, 28 had exposure to bevacizumab, and 43 had received pelvic radiation therapy.

The patients had a median OS of 6.2 months, and 19 of 50 remained alive for 12 months, resulting in a 12-month survival of 38%. Comparison of the attained and benchmark survival values showed a statistically significant outcome (P = .02). One patient achieved a complete response with AXAL and 15 had stable disease.

HPV genotyping for 41 patients showed that 35 tested positive for the virus, including 33 evaluable patients, 16 who tested positive for HPV-16 and 17 positive for HPV-18. The HPV-16­—positive subgroup had a 12-month survival of 44% and median OS of 17.8 months for those patients alive at 12 months. The HPV-18–positive subgroup had a 12-month OS of 41% and median OS of 15.7 months among those alive at 12 months.

Leath said the safety profile of AXAL was consistent with previous clinical experience, and the immunotherapy was generally well tolerated. Most adverse events were infusion-related, low-grade, and transient.

The next step in clinical evaluation of AXAL will be a phase III trial as adjuvant monotherapy to prevent recurrence in patients with high-risk cervical cancer treated with chemoradiation.

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