Phase II trial of albumin-bound paclitaxel and granulocyte macrophage colony-stimulating factor as an immune modulator in recurrent platinum resistant ovarian cancer

BackgroundGranulocyte macrophage colony-stimulating factor (GM-CSF) stimulates immunity via recruitment of antigen presenting cells and tumor specific T-cell stimulation. Albumin-bound paclitaxel (nab-paclitaxel) followed by GM-CSF may enhance antitumor responses and prolong remissions in ovarian cancer. Immune phenotypes present before treatment may identify responders to chemo-immunotherapy.MethodsRecurrent platinum-resistant ovarian, peritoneal, or fallopian tube cancer patients received nab-paclitaxel, 100 mg/m² days 1, 8, 15 followed by GM-CSF 250 μg days 16–26 every 28 days for 6 planned cycles. The primary endpoint was remission duration compared to immediate prior remission. Peripheral blood was evaluated by flow cytometry and interferon-γ ELISPOT.ResultsTwenty-one patients were enrolled. Six patients (29%) achieved a biochemical complete response and 9 (43%) a partial response for an overall response rate of 72%. Median time to progression was 4 months and 10% of patients achieved longer remissions than the immediate prior regimen. Median overall survival (OS) was 16.8 months. Fewer myeloid derived suppressor cells (MDSC) at enrollment significantly associated with complete response (p = 0.05). T-cell responses to IGF1R-p1332–1346 (r = 0.827, p = 0.0003) and IGF1R-p1242–1256 (r = 0.850, p = 0.0001) during treatment correlated with time to progression.ConclusionsNab-paclitaxel combined with GM-CSF demonstrated biochemical responses in a majority of patients, although responses were not sustained. This combination did not demonstrate an advantage in OS over prior studies of nab-paclitaxel monotherapy. Agents that modulate MDSC should be studied as potential adjuvants to therapy. Strategies to expand T cells recognizing tumor-associated antigens biologically significant in ovarian cancer should also continue to be investigated.