Avastin-Novel Therapy Combo Induces Durable Responses in Subgroup of Patients With Ovarian Cancer

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The combination may offer patients with recurrent, platinum-agnostic ovarian cancer a more effective, non-platinum-based treatment option.

Treatment with the combination of IMGN853 (mirvetuximab soravtansine) and Avastin (bevacizumab) was associated with durable responses and improved survival rates in patients with recurrent, platinum agnostic ovarian cancer, according to recent study findings.

“These data add to the previously reported (findings) and support the use of mirvetuximab as the partner of choice for (Avastin) in patients with high (folate receptor alpha) ovarian cancer following the use of platinum-based treatments,” lead study author Dr. David M. O'Malley director of the Division of Gynecologic Oncology at The Ohio State University Comprehensive Cancer Center – James, said during a presentation of the findings at the 2021 American Society of Clinical Oncology Annual Meeting. “Further development of mirvetuximab in combination with (Avastin) is warranted.”

Recent developments with the addition of PARP inhibitors to the treatment regimen for patients with recurrent ovarian cancer has produced an increasing number of patients for whom a non-platinum-based regimen would be appropriate. Moreover, previous results have shown that the use of IMGN853 was associated with promising results in patients with platinum-resistant ovarian cancer.

As a result, this trial set out to assess the combination of IMGN853 and Avastin as a non-platinum-based treatment option to address the unmet need for this patient population. Patients (median age, 60 years) with recurrent ovarian cancer who had previously received up to three prior treatment regimens were enrolled onto the study. Patients were allowed to have received previous treatment with Avastin. Most of the 60 patients enrolled onto the trial had epithelial ovarian cancer (68%), while the rest had either fallopian tube cancer (25%) or primary peritoneal cancer (7%).

The study results indicated that the overall response rate (or the rate of a measurable response to the treatment) was 50% among all patients enrolled onto the study. Moreover, patients who had high folate receptor alpha (33 patients) expression had an overall response rate of 64% vs 33% in patients with medium levels of high folate receptor alpha expression (27 patients). Patients with platinum-resistant ovarian cancer (17 patients) had an overall response rate of 59%, while patients with platinum-sensitive disease (16 patients) had an overall response rate of 69%. Additionally, 97% of patients demonstrated a reduction in tumor burden following treatment.

The median duration of response (length of time a tumor responds to treatment without the cancer growing or spreading) among all patients was 9.7 months, while those with medium and high folate receptor alpha expression had a median duration of response of 8.3 months and 11.8 months, respectively. Additionally, patients with platinum-resistant disease had a median duration of response of 9.4 months, and the platinum-sensitive subgroup had a median duration of response of 12.7 months.

“These deep responses are rapid and durable … in patients with platinum-resistant and platinum-sensitive disease,” O’Malley said. “Many of these durable responses continue beyond six to 12 months, with some patients’ responses lasting more than two years.”

Moreover, patients whose tumors had medium and high folate receptor alpha expression had a median progression-free survival (time during and after treatment when the patient lives without disease progression) of 5.4 months, and 10.6 months, respectively. The high folate receptor alpha subgroup, specifically, demonstrated a 6-month progression-free survival rate of 80%, and a 12-month rate of 42%. Additionally, patients within the high folate receptor alpha cohort who had platinum-sensitive and platinum-resistant ovarian cancer had a median progression-free survival of 13.3 months and 9.7 months, respectively.

“The (progression-free survival), (much) like the data from the (overall response rate) and (duration of response), demonstrated that patients with high (folate receptor alpha) benefit the most from the combination of mirvetuximab and (Avastin),” O’Malley explained.

Most side effects associated with treatment were mild, the most common being gastrointestinal side effects, as well as ocular side effects that could be managed using eye drops. More severe side effects were infrequent, the most notable of which were hypertension (17%), and neutropenia (low count of white blood cells, neutrophils; 13%). In total, 30% of patients discontinued treatment with IMGN853 and Avastin due to treatment-related side effects, and discontinuations occurred after a median of 13 cycles of treatment.

Twenty-three percent of patients discontinued treatment with IMGN853, and 18% discontinued Avastin. The most common side effects associated with the treatment were diarrhea (62%), blurred vision (60%), fatigue (60%) and nausea (57%).

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