Opdivo-Avastin Combo Safe, Has Strong Activity in Relapsed Ovarian Cancer Patients, Phase 2 Trial Shows

A combination of Opdivo (nivolumab) and Avastin (bevacizumab) is safe and has strong clinical activity in women with relapsed ovarian cancer, especially among those whose tumors were sensitive to platinum-based chemotherapy, a Phase 2 clinical trial shows.

The study, “Assessment of Combined Nivolumab and Bevacizumab in Relapsed Ovarian Cancer: A Phase 2 Clinical Trial,” was published in JAMA Oncology.

Immune checkpoint inhibitors are therapies based on the principle of removing the “brakes” of our immune system, to use the power of the body’s immune system to fight cancer faster and more effectively.

Opdivo, by Bristol-Myers Squibb, is included in this group of therapies, and works by binding to a protein found on the surface of immune cells called programmed cell death (PD-1) and prevent it from interacting with its ligands, PD-L1 and PD-L2, which are produced by cancer cells. This disruption in the PD-1 signaling pathway allows immune cells to find and eliminate cancer cells.

“Immune checkpoint inhibitor therapies have transformed cancer treatment in certain solid malignant tumors, such as melanoma and renal cell carcinomas,” the researchers stated.

However, when used alone, PD-1 and PD-L1 inhibitors have shown limited activity treating women with ovarian cancer. A possible alternative to boost their effectiveness would be combining them with other medications that use different mechanisms to eliminate cancer cells.

Anti-angiogenic therapies (medications designed to limit tumors’ blood supply to restrict their growth) such as Avastin, developed by Genentech, have been shown to increase the effectiveness of immune checkpoint inhibitors in different types of solid tumors.

In this study, investigators reported the findings of a Phase 2 trial (NCT02873962) designed to assess the clinical activity of a combination therapy of Opdivo and Avastin in women with ovarian cancer whose disease returned within a year of completing their last course of platinum-based chemotherapy.

The trial enrolled 38 women with relapsed ovarian cancer, including 18 with platinum-resistant and 20 with platinum-sensitive cancer, from two clinical sites in the U.S., between Feb. 8 and Dec. 29, 2017. All women participating in the study had received one to three prior lines of therapy before enrolling in the trial.

All study participants received Opdivo (240 mg) and Avastin (10 mg/kg) once every two weeks, both delivered as into-the-vein infusions.

The study’s main goal was to assess the percentage of women who responded to treatment (a measure called objective response rate). Secondary goals included assessing the percentage of patients with platinum-resistant or platinum-sensitive disease and different levels of tumoral PD-L1 who responded to treatment, the time women lived without showing signs of disease progression, and safety assessments.

Of the 38 women enrolled in the trial, 11 (28.9%) had a confirmed response to the Opdivo-Avastin combo therapy, and one had an unconfirmed response to treatment. The percentage of women who responded to the combination therapy was higher among those with platinum-sensitive disease (40%), than among those with platinum-resistant cancer (16.7%).

The median time women lived until showing signs of disease progression was 8.1 months, but this outcome was also better in platinum-sensitive patients than in platinum-resistant ones — 9.4 months vs. 5.3 months.

From the 36 tumor samples that were examined for levels of PD-L1, 22 (61.1%) tumors had less than 1% of PD-L1, and 14 (38.9%) had more than 1% of PD-L1. Ten women who responded to treatment had lower levels of PD-L1, while the remaining two had higher levels of PD-L1.

Almost all women participating in the study (89.5%) experienced at least one side effect of treatment, and almost a fourth (23.7%) had a severe (grade 3), life-threatening (grade 4), or fatal (grade 5) adverse event to therapy.

“The results of our trial suggest that a nivolumab and bevacizumab combination was feasible and well tolerated in patients with ovarian cancer,” the researchers said.

“Although the study met its primary statistical endpoint for overall response, with an ORR of 28.9%, examination of the response rates by platinum status suggests that this combination strategy may have the greatest promise in platinum-sensitive disease, while alternative strategies to enhance immunotherapy may still be required in the platinum-resistant setting,” they wrote.