Nivolumab Active in Advanced Gynecologic Cancers

Antoine Hollebecque, MD

In phase I/II results from CheckMate-358, nivolumab (Opdivo) demonstrated clinical activity in women with recurrent/metastatic cervical cancer, and was active to a lesser extent in vaginal and vulvar cancers.

Antoine Hollebecque, MD, with Institut de Cancérologie Gustave Roussy in Villejuif, France, presented the results at the 2017 ASCO Annual Meeting. He said the overall response rate (ORR) across the 3 tumor types was was 20.8% (95% CI, 7.1-42.2) and the disease control rate (DCR) was 70.8%. Median follow-up was 31 weeks.

“Nivolumab demonstrated encouraging clinical activity in patients with recurrent or metastatic cervical, vagina, and vulvar cancers,” Hollegecque said. “These data support further evaluation of nivolumab in these patients, including in combination with other therapies.”

Three-month progression-free survival (PFS) was 73.9%. Median PFS was 5.5 months (95% CI, 3.5-not reached). Six-month overall survival (OS) was 87.1%. Median OS was not reached.

Hollegecque said that as much as 69% of vulvar cancers, 75% of vaginal cancers, and more than 90% of cervical cancers can be attributed to HPV. In the recurrent/metastatic setting, ORR is 0% to 14% for these cancers.

“HPV can evade host immune surveillance through increased expression of PD-L1, enabling viral persistence and the development of malignant lesions,” he said. “Nivolumab, a PD-1 inhibitor, has demonstrated antitumor activity in several tumor types and the role of immunotherapy is evolving in gynecological malignancies.”

Researchers enrolled 24 patients into the gynecologic arm of the CheckMate-358 trial from October 2015 to February 2016. Nineteen patients (79.2%) had cervical cancer and 5 (20.8%) had vaginal or vulvar cancer. Eligible patients had an ECOG performance score of 0 to 1 and ≤2 prior systemic therapies for relapsed/metastatic disease.

Fourteen patients (58.3%) were positive for HPV. HPV status was unknown for the 10 remaining patients (41.7%).

All patients were treated with 240 mg of nivolumab every 2 weeks until progression or unacceptable toxicity.

While the overall DCR was 70.8%, nivolumab induced stronger responses in women with cervical cancer.

At the July 2016 data cutoff, there was 1 complete response (CR) and 4 partial responses (PR), all among patients with cervical cancer (ORR = 26.3%). The best response among patients with vulvar or vaginal cancer was stable disease (80%).

Duration of response was not reached in any group, but Hollegecque said all objective responses lasted at least 6 months.

“At the data cutoff, the 5 patients with an objective response were still ongoing,” he said. “Nine out of 24 patients were still free from progression.”

ORR was 28.6% for patients who received nivolumab in first-line (n =7) and 17.6% among those who received at least 1 previous systemic treatment (n = 17). DCR was 71.4% and 70.6%, respectively.

PD-L1 expression was ≥1% in 10 patients (41.7%) and ≤1% in 3 patients (12.5%). Ten patients were not tested for PD-L1 expression and 1 patient was not evaluable.

ORR was 20% (95% CI, 2.5-55.6) among patients in the PD-L1 expressing group with 1 CR, 1 PR and 6 patients with stable disease, for a DCR of 80%. ORR was 33.3% (95% CI, 0.8-90.6) in the nonexpressing group. One patient each had PR and stable disease, for a DCR of 66.7%.

Among HPV-positive patients, there were 4 PRs (28.6%) and 4 patients with stable disease. ORR was 28.6% and DCR was 57.1%. Among patients with unknown HPV-status, there was 1 CR and 8 patients with stable disease. ORR was 10% and DCR was 90.0%.

Seventeen patients (70.8%) experienced a treatment-related adverse event (AE) and 3 (12.5%) experienced a grade 3/4 treatment-related AE, including diarrhea, hyponatremia, syncope, and hepatocellular injury. There were no treatment-related deaths.

“The observed safety profile was manageable and consistent with previous results seen with nivolumab monotherapy,” Hollegecque said.

Hollegecque A, Meyer T, Moore KN, et al. An open-label, multicohort, phase I/II study of nivolumab in patients with virus-associated tumors (CheckMate 358): Efficacy and safety in recurrent or metastatic (R/M) cervical, vaginal, and vulvar cancers. J Clin Oncol 35, 2017 (suppl; abstr 5504).