Researchers Discuss Evolution of Immunotherapy Approaches for Gynecologic Malignancies

CHICAGO — Immunotherapy approaches are evolving for all types of gynecologic malignancies, including ovarian, cervical, and endometrial cancers, according to a poster discussion at the 2016 American Society of Clinical Oncology (ASCO) Annual Meeting.¹

In this session, Rebecca S. Kristeleit, BSc, MRCP, PhD, consultant medical oncologist at University College London Cancer Institute, reviewed 3 posters evaluating immunotherapies for the treatment of gynecologic cancers.

The first study evaluated a polyvalent vaccine-KLH conjugate plus OPT-821 compared with OPT-821 alone in 171 patients with epithelial ovarian, fallopian tube, or peritoneal cancer who were in second or third remission.²

Results showed there was no significant difference in median progression-free survival between the 2 arms (HR, 0.98). Median overall survival was 47 months in the OPT-821 control arm, while it had not yet been reached in the vaccine arm.²

“This study’s strengths were that it had well-balanced groups, a relatively homogenous population; it was a randomized phase 2 trial; and recruitment was faster than expected,” Dr Kristeleit said. “However, its weaknesses included a long development path, very limited immunological response data, no immunological pre-selection, and competing agents.”

Therefore, Dr Kristeleit believed that vaccine therapy with an immunoadjuvant is a feasible approach but added that more data on immunogenicity is needed to fully evaluate it in this treatment setting.¹

The second poster presented was a phase 2 trial that assessed the activity and tolerability of ADXS11-001, a live attenuated Listeria monocytogenes(Lm)-listeriolysin O immunotherapy that targets HPV-transformed cells, inducing antitumor T-cell immunity, and breaking immune tolerance in the tumor microenvironment.³

In the single-arm study, investigators enrolled 50 patients with squamous or non-squamous persistent/recurrent metastatic cervical cancer who had received at least 1 line of prior therapy in the noncurative setting. All patients received ADXS11-001 monotherapy intravenously months for 3 months. Results showed that the 12-month survival rate 38.5%, thus achieving the primary endpoint, and immunotherapy was associated with grade 3 to 4 toxicity in 19% of patients.³

Although this study achieved it primary end point, results were only from stage 1. There will be a different schedule and more patients have a history of prior bevacizumab therapy in stage 2. Although this is a promising therapeutic option with encouraging signals, a randomized phase 3 trial in relapsed disease in needed to confirm its efficacy, noted Dr Kristeleit.

Finally, Dr Kristeleit discussed preliminary results from the phase 1b KEYNOTE-028 trial of the immune checkpoint inhibitor pembrolizumab in advanced endometrial cancer. For the study, 24 heavily pretreated patients were enrolled to receive pembrolizumab 10 mg/kg intravenously every 2 weeks for up to 24 months or until confirmed disease progression or unacceptable toxicity.⁴

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Investigators found that pembrolizumab was well tolerated and no patients discontinued treatment as a result of toxicity. In terms of efficacy, the objective response rate was 13%. Although there were no complete responses, the responses were strikingly durable.⁴

“Immune checkpoint inhibitors have the potential to significantly improve treatment options for endometrial cancer,” Dr Kristeleit concluded. “Selecting for patients with high microsatellite instability may augment the response rate and is feasible.”                            

Reference

1. Kristeleit RS. Over the horizon: novel immunotherapies in gynecologic cancers. Presented at: 2016 American Society of Clinical Oncology (ASCO) Annual Meeting; June 3-7, 2016; Chicago, IL.
2. Sabbatini P, Chen L-M, Lucci JA, et al. A phase II randomized, double-blind trial of a polyvalent vaccine-KLH conjugate (NSC 748933 IND# 14384) + OPT-821 versus OPT-821 in patients with epithelial ovarian (EOC), fallopian tube, or peritoneal cancer who are in second or third complete remission. J Clin Oncol. 2016; 34 (suppl; abstr 5517).
3. Huh WK, Dizon DS, Powell MA, et al. ADXS11-001 immunotherapy in squamous or non-squamous persistent/recurrent metastatic cervical cancer: Results from stage I of the phase II GOG/NRG0265 study. J Clin Oncol. 2016; 34 (suppl; abstr 5516).
4. Ott PA, Bang Y-J, Berton-Rigaud D, et al. Pembrolizumab in advanced endometrial cancer: Preliminary results from the phase Ib KEYNOTE-028 study. J Clin Oncol. 2016; 34 (suppl; abstr 5581).