Treatment with nivolumab (Opdivo) led to durable responses and stable disease in a majority of women with relapsed or metastatic cancers caused by human papillomavirus (HPV) infection, according to the results of a phase 1/2 clinical trial—CheckMate-358.
Overall, 5 of 24 patients in the study attained objective responses, and an additional 12 had stable disease, resulting in a disease control rate of 71%. All 5 responses, including 1 complete response, were in 19 patients with HPV-associated cervical cancer.
All 5 objective responses were ongoing at the data cutoff after a median follow-up of 31 weeks, reported Antoine Hollebecque, MD, Consultant Oncologist, Gustave Roussy Cancer Institute, Villejuif, France, at the 2017 ASCO annual meeting.
“Nivolumab demonstrated encouraging clinical activity in patients with recurrent or metastatic cervical, vaginal, and vulvar cancers. The safety profile of nivolumab was manageable and consistent with previous results seen with nivolumab monotherapy in other tumor types,” said Dr Hollebecque.
Recurrent and metastatic cancers of the cervix, vagina, and vulva have limited treatment options and poor prognosis. Available second-line therapies are associated with objective response rates of 0% to 14% and median progression-free survival (PFS) of 2 to 4 months.
HPV infection causes approximately 90% of cervical cancers, 75% of vaginal cancers, and 69% of vulvar cancers. HPV can evade host immune surveillance by increased expression of PD-L1, enabling viral persistence and malignant evolution, Dr Hollebecque noted. Previous studies identified PD-L1 as a marker of HPV infection in the cervix and demonstrated that the ligand is upregulated in cervical cancer.
“Nivolumab, a PD-1 inhibitor, has demonstrated antitumor activity in several tumor types, and the role of immunotherapy, including PD-1 inhibition, is evolving in gynecologic malignancies,” said Dr Hollebecque.
CheckMate-358 is an ongoing, phase 1/2 multicohort clinical trial evaluating nivolumab in various types of virus-associated cancers, including Epstein-Barr virus–positive gastric cancer, HPV-positive squamous-cell cancer of the head and neck, Merkel-cell carcinoma, and nasopharyngeal carcinoma, as well as cervical, vaginal, and vulvar cancers. Dr Hollebecque reported findings from the gynecologic cancer cohort.
Eligible patients had received ≤2 previous lines of therapy for recurrent or metastatic disease, had at least 1 target lesion, and had an Eastern Cooperative Oncology Group performance status 0 or 1. Patients were not selected on the basis of PD-L1 expression.
All patients enrolled in CheckMate-358 received nivolumab 240 mg every 2 weeks until disease progression or unacceptable toxicity. Imaging for response assessment occurred every 8 weeks during the first year, then every 12 weeks. The primary end point was objective response. The secondary end points included duration of response, PFS, and overall survival.
Cervical cancer accounted for 19 of the 24 patients in the gynecologic cancer cohort. Seven patients had no previous therapy for recurrent or metastatic disease, 10 had 1 previous therapy, and 7 patients had 2 previous lines of therapy. A total of 10 patients had tumors with PD-L1 expression ≥1%, 3 had lower levels of expression, 10 patients were not tested, and 1 patient was not evaluable.
The cervical cancer subgroup had an overall response rate of 26.4%; none of the 5 patients with vaginal/vulvar cancer achieved objective responses. One patient with vaginal/vulvar cancer met the tumor reduction criteria for a partial response, but had a new lesion, and a second patient with vaginal/vulvar cancer had an unconfirmed partial response.
Of the 5 patients with vaginal/vulvar cancer, 4 had stable disease during treatment with nivolumab, as did 8 patients with cervical cancer. Approximately 50% of all the patients had some degree of tumor shrinkage with nivolumab.
Assessment of response by previous therapy showed that 2 of 7 patients who had no previous therapy had partial responses, and 3 others had stable disease. Of the 17 patients who had ≥1 previous lines of therapy for recurrent or metastatic disease, 1 had a complete response, 2 had partial responses, and 9 had stable disease.
Of all patients, 75% remained alive without progression at 3 months; the median PFS was 5.5 months.
The most common adverse events (any grade) were diarrhea and fatigue (4 cases each); arthralgia and decreased appetite (3 cases each); and pruritus, dry eye, and hypothyroidism (2 cases each). The only grade 3 or 4 adverse event was a single case of diarrhea.
“These data support further evaluation of nivolumab in these patients, including in combination with other therapies,” Dr Hollebecque concluded.