Deanna Teoh, MD, MS
The prognosis for women with recurrent or metastatic cervical cancer after treatment failure is notoriously poor, but immunotherapy agents may offer longer survival for this population, Deanna Teoh, MD, MS, said at the 2019 SGO Annual Winter Meeting.1
To date, bevacizumab (Avastin) has produced the best results, with a median overall survival (OS) of 7.3 months in this patient population. Clinical trial data suggests that immunotherapeutic agents can offer equivalent or superior median OS.
“Immunotherapy is promising for the treatment of advanced or recurrent cervical cancer, but I think that we really have to figure out which patients or which tumors are best suited for different therapies,” said Teoh, assistant professor in the Division of Gynecologic Oncology at the University of Minnesota Medical School and medical director of gynecologic oncology at Regions Cancer Care Center in St. Paul, Minnesota.
In phase II data presented at the 2014 ASCO Annual Meeting, axalimogene filolisbac (AXAL)—a live attenuated Listeria monocytogenes immunotherapy agent bioengineered to induce antitumor T-cell immunity and break immune tolerance in the tumor microenvironment—improved median OS among 110 Indian women with recurrent cervical cancer who had previously received chemotherapy, radiotherapy or both. Treatment resulted in a median OS of 8.28 months, with a 12-month OS rate of 30.9% and an overall response rate of 17.1%. The addition of cisplatin did not result in a significant improvement in OS (P
= .9981) in 69 evaluable patients.2
Axalimogene filolisbac was further evaluated in this patient population in the phase II GOG/NRG-0265 study. The immunotherapy agent induced an unprecedented 1-year survival rate of 38%, a 52% improvement over the calculated survival. The median OS was 6.2 months and 32% of patients achieved disease control based on investigator assessment of best response of the 50 evaluable patients.3
In a January 2018 interview with OncLive
, Sharad Ghamande, MD, director for gynecological oncology at Augusta University, said cervical cancer is the most attractive target for immunotherapy among gynecologic cancers.
“If you look at the genesis of cervical cancer, there is always an HPV infection. The immune system in most cases, especially when we are younger, takes care of the infection,” he said. “However, if it is persistent as we get older, it then causes cancerous changes. HPV is a target that is always expressed, making it a very potent target that we can exploit either by a vaccine or checkpoint inhibition.”
Teoh said that one of the most exciting things about immunotherapeutic agents is that they are generally well tolerated. The only grade ≥3 treatment-related adverse event (TRAE) recorded in GOG/NRG-0265 was grade 3 anemia in 10% of patients.
Based on these findings, axalimogene filolisbac is now being investigated in the ongoing global phase III AIM2CERV (NCT02853604) trial as adjuvant monotherapy to prevent recurrence in patients with locally advanced cervical cancer treated with chemoradiation.
Patients are randomly assigned 2:1 to axalimogene filolisbac or placebo. The experimental cohort will receive 3 doses of axalimogene filolisbac every 3 weeks during the primary phase, followed by a maintenance phase where the drug is administered every 2 months for 1 year.
The current trial design has a planned sample size of 450 patients to maintain adequate statistical power over a broader range of survival outcomes, as well as a preplanned interim analysis (IA) of safety and efficacy. Advaxis, the developer of axalimogene filolisbac, is considering accelerating the IA timeline and establishing a more stringent futility boundary. The company expects to finalize the redesign in the next few months.
The FDA lifted a clinical hold on a phase I/II study for axalimogene filolisbac in combination with durvalumab (Imfinzi) for the treatment of patients with advanced, recurrent, or refractory cervical cancer and HPV-associated head and neck cancer in July 2018. The agency applied the hold in March following a report of a patient who died of acute respiratory failure after 9 months of combination therapy. Advaxis agreed to new guidelines for the early detection and treatment of such rare adverse events.
Enrollment in AIM2CERV was not affected by the clinical hold.
Immune Checkpoint Inhibitors
Investigators are evaluating immune checkpoint inhibitors (ICIs) for the treatment of cervical cancer in several clinical trials including CheckMate 358 and KEYNOTE-028 and -158. Results are also pending for the phase II GY-007 trial evaluating nivolumab (Opdivo) for persistent, recurrent, or metastatic cervical cancer.