番茄社区

CHICAGO -- Results from a study using the experimental monoclonal antibody drug abagovomab to protect women with advanced ovarian cancer from recurrence have been disappointing, researchers reported here.

In the primary endpoint for the trial, progression-free survival, there was no difference in time before progression -- 13.2 months -- between patients treated with abagovomab and those treated with placebo (P=0.675), said Jacobus Pfisterer, MD, PhD, professor of medicine at Klinikum Solingen, Germany.

Pfisterer presented the results of the Monoclonal Antibody Immunotherapy for Malignancies of the Ovary by Subcutaneous Abagovomab (MIMOSA) trial here at the annual meeting of the American Society of Clinical Oncology.

The secondary endpoint of overall survival also showed no distinction between the treatment groups and placebo patients. There were 171 deaths among the patients treated with abagovomab (28.8%), which compared with 80 deaths or 27.1% of the patients on placebo (P=0.727).

The researchers reported that 93% of the women in the study who were assigned to abagovomab survived for one year, compared with 95% of the patients on placebo. After three years, 67% of the women on abagovomab were alive compared with 68% of those on placebo.

Pfisterer noted that treatment with abagovomab was successful in eliciting a specific immunologic response soon after the induction period, and he noted that the drug was very well tolerated. But those positive aspects of the trial did not equate to efficacy.

"Abagovomab maintenance treatment after debulking surgery and successful platinum and taxane first-line chemotherapy did not prolong progression-free survival in advanced ovarian cancer," he said in a late-breaker report given during a packed plenary session.

The invited discussant for the MIMOSA trial, George Coukos, MD, PhD, professor of gynecologic oncology at the University of Pennsylvania Philadelphia, suggested that the target of abagovomab – the CA-125 receptor – may not be the best avenue to approach ovarian cancer recurrence.

"CA-125-targeted immunotherapy based on antibody approaches does not appear to be a useful clinical strategy," Coucos said. He noted that oregovomab -- a cousin of abagovomab – also failed to produce positive results in ovarian cancer.

But he wasn't willing to give up on immunotherapy in the disease. "Multivalent immunization may be more successful; immunomodulation is likely to play an important role," he said.

In the MIMOSA study, Pfisterer and colleagues enrolled 888 patients between December 2006 and December 2008. During the 48 month double-blind period of the trial, 593 women were treated with abagovomab and 295 women were assigned to treatment in the placebo arm.

The women in the study were diagnosed with histological and CA-125-confirmed stage III-IV epithelial ovarian, fallopian tube, or primary peritoneal cancer. They had to have a complete clinical response defined as normal physical examination, no symptoms suggestive of persistent cancer, no definitive evidence of disease by computer-assisted tomography scans of the abdomen and pelvis; negative chest x-rays, and normal CA-125 levels. They also had undergone definitive debulking surgery followed by six to eight cycles of chemotherapy.

If the women were determined to have a complete response to therapy, they were assigned to either abagovomab 2 mg/ml subcutaneously or a placebo suspension delivered by subcutaneous injections. They continued treatment every other week for six weeks, then once a month until 21 months after enrollment of the last patients.

The average age of the women in the study was 56.4 years; about 80% of the women had serous or papillary histology. All but two women had performance status of 0 or 1 -- performance status of 2 or less made a woman eligible for inclusion in the study.