ASCO: Ascites may salvage trebananib in recurrent ovarian cancer

CHICAGO – Disappointing topline overall survival results from TRINOVA-1 reported late last year dashed enthusiasm for trebananib in recurrent ovarian cancer, but a subgroup analysis suggests the anti-angiopoietin therapy may yet have a use.

In patients with ascites at baseline, adding trebananib to paclitaxel provided a nearly 30% survival advantage, increasing median overall survival from 12.3 months to 14.5 months (hazard ratio, 0.72; P = .011), Dr. Bradley Monk reported at the annual meeting of the American Society of Clinical Oncology.

There was no overall survival benefit in the full intent-to-treat population. Median overall survival was 18.3 months for single-agent paclitaxel and 19.3 months for the combination (HR, 0.95; P = .52).

Presence of ascites at baseline was a prespecified subgroup, stressed Dr. Monk, director of gynecologic oncology at St. Joseph’s Hospital, Phoenix, who noted that 32% of women fell into this subgroup (295/919 patients).

Women with and without ascites at baseline had the same age, primary tumor type, number of prior lines of therapy, and prior antiangiogenic therapy, although more patients with ascites had a platinum-free interval of less than 6 months (58% vs. 49%).

“So they were a poor prognosis group not only because of the ascites, but they had more platinum-resistant disease,” he said.

The TRINOVA-1 trial previously demonstrated a significant increase in the primary endpoint of median progression-free survival (PFS) from 5.4 months to 7.2 months when adding weekly trebananib to weekly paclitaxel (HR, 0.66; P < .001).

At baseline, about 40% of patients had received one or two prior lines of prior therapy and roughly a fourth received three prior lines. Patients received an average of 2.2 lines of additional anticancer therapy after progression on study.

An exploratory analysis of PFS after subsequent therapy revealed a median PFS of 12.5 months in the trebananib group vs. 10.9 months in the paclitaxel group (HR, 0.85; P = .024), Dr. Monk said.

Discussant Dr. Don Dizon, with Massachusetts General Hospital in Boston, said the results provide a strong signal of benefit in women with recurrent ovarian cancer and ascites, but can’t be considered definitive without further study.

Both men observed that treatment with trebananib plus paclitaxel was associated with an increase in adverse events. Trebananib was associated with 32% more localized edema of any grade (59% vs. 27%), but most of these events were grade 1 or 2, Dr. Monk said. The paclitaxel and trebananib groups had similar grade 3 (56% vs. 60%) and grade 4 events (12% vs. 12%) and patient-reported Functional Assessment of Cancer Therapy-Ovarian (FACT-O) scores at week 25.

Amgen funded the study. Dr. Monk reported having no conflicts of interest. Dr. Dizon reported employment and an advisory or consulting role with UpToDate and institutional research funding from Aeterna Zentaris and GlaxoSmithKline.

[email protected]

On Twitter @pwendl

CHICAGO – Disappointing topline overall survival results from TRINOVA-1 reported late last year dashed enthusiasm for trebananib in recurrent ovarian cancer, but a subgroup analysis suggests the anti-angiopoietin therapy may yet have a use.

In patients with ascites at baseline, adding trebananib to paclitaxel provided a nearly 30% survival advantage, increasing median overall survival from 12.3 months to 14.5 months (hazard ratio, 0.72; P = .011), Dr. Bradley Monk reported at the annual meeting of the American Society of Clinical Oncology.

There was no overall survival benefit in the full intent-to-treat population. Median overall survival was 18.3 months for single-agent paclitaxel and 19.3 months for the combination (HR, 0.95; P = .52).

Presence of ascites at baseline was a prespecified subgroup, stressed Dr. Monk, director of gynecologic oncology at St. Joseph’s Hospital, Phoenix, who noted that 32% of women fell into this subgroup (295/919 patients).

Women with and without ascites at baseline had the same age, primary tumor type, number of prior lines of therapy, and prior antiangiogenic therapy, although more patients with ascites had a platinum-free interval of less than 6 months (58% vs. 49%).

“So they were a poor prognosis group not only because of the ascites, but they had more platinum-resistant disease,” he said.

The TRINOVA-1 trial previously demonstrated a significant increase in the primary endpoint of median progression-free survival (PFS) from 5.4 months to 7.2 months when adding weekly trebananib to weekly paclitaxel (HR, 0.66; P < .001).

At baseline, about 40% of patients had received one or two prior lines of prior therapy and roughly a fourth received three prior lines. Patients received an average of 2.2 lines of additional anticancer therapy after progression on study.

An exploratory analysis of PFS after subsequent therapy revealed a median PFS of 12.5 months in the trebananib group vs. 10.9 months in the paclitaxel group (HR, 0.85; P = .024), Dr. Monk said.

Discussant Dr. Don Dizon, with Massachusetts General Hospital in Boston, said the results provide a strong signal of benefit in women with recurrent ovarian cancer and ascites, but can’t be considered definitive without further study.

Both men observed that treatment with trebananib plus paclitaxel was associated with an increase in adverse events. Trebananib was associated with 32% more localized edema of any grade (59% vs. 27%), but most of these events were grade 1 or 2, Dr. Monk said. The paclitaxel and trebananib groups had similar grade 3 (56% vs. 60%) and grade 4 events (12% vs. 12%) and patient-reported Functional Assessment of Cancer Therapy-Ovarian (FACT-O) scores at week 25.

Amgen funded the study. Dr. Monk reported having no conflicts of interest. Dr. Dizon reported employment and an advisory or consulting role with UpToDate and institutional research funding from Aeterna Zentaris and GlaxoSmithKline.

[email protected]

On Twitter @pwendl

CHICAGO – Disappointing topline overall survival results from TRINOVA-1 reported late last year dashed enthusiasm for trebananib in recurrent ovarian cancer, but a subgroup analysis suggests the anti-angiopoietin therapy may yet have a use.

In patients with ascites at baseline, adding trebananib to paclitaxel provided a nearly 30% survival advantage, increasing median overall survival from 12.3 months to 14.5 months (hazard ratio, 0.72; P = .011), Dr. Bradley Monk reported at the annual meeting of the American Society of Clinical Oncology.

There was no overall survival benefit in the full intent-to-treat population. Median overall survival was 18.3 months for single-agent paclitaxel and 19.3 months for the combination (HR, 0.95; P = .52).

Presence of ascites at baseline was a prespecified subgroup, stressed Dr. Monk, director of gynecologic oncology at St. Joseph’s Hospital, Phoenix, who noted that 32% of women fell into this subgroup (295/919 patients).

Women with and without ascites at baseline had the same age, primary tumor type, number of prior lines of therapy, and prior antiangiogenic therapy, although more patients with ascites had a platinum-free interval of less than 6 months (58% vs. 49%).

“So they were a poor prognosis group not only because of the ascites, but they had more platinum-resistant disease,” he said.

The TRINOVA-1 trial previously demonstrated a significant increase in the primary endpoint of median progression-free survival (PFS) from 5.4 months to 7.2 months when adding weekly trebananib to weekly paclitaxel (HR, 0.66; P < .001).

At baseline, about 40% of patients had received one or two prior lines of prior therapy and roughly a fourth received three prior lines. Patients received an average of 2.2 lines of additional anticancer therapy after progression on study.

An exploratory analysis of PFS after subsequent therapy revealed a median PFS of 12.5 months in the trebananib group vs. 10.9 months in the paclitaxel group (HR, 0.85; P = .024), Dr. Monk said.

Discussant Dr. Don Dizon, with Massachusetts General Hospital in Boston, said the results provide a strong signal of benefit in women with recurrent ovarian cancer and ascites, but can’t be considered definitive without further study.

Both men observed that treatment with trebananib plus paclitaxel was associated with an increase in adverse events. Trebananib was associated with 32% more localized edema of any grade (59% vs. 27%), but most of these events were grade 1 or 2, Dr. Monk said. The paclitaxel and trebananib groups had similar grade 3 (56% vs. 60%) and grade 4 events (12% vs. 12%) and patient-reported Functional Assessment of Cancer Therapy-Ovarian (FACT-O) scores at week 25.

Amgen funded the study. Dr. Monk reported having no conflicts of interest. Dr. Dizon reported employment and an advisory or consulting role with UpToDate and institutional research funding from Aeterna Zentaris and GlaxoSmithKline.

[email protected]

On Twitter @pwendl