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

MDSC (myeloid-derived suppressor cells) are a heterogenous group of immune cells from the myeloid lineage (a family of cells that originate from bone marrow stem cells). MDSCs strongly expand in pathological situations such as chronic infections and cancer, as a result of an altered haematopoiesis (def.: process of blood cell formation.)
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abstract:
Phase II trial of albumin-bound paclitaxel and granulocyte macrophage colony-stimulating factor as an immune modulator in recurrent platinum resistant ovarian cancer
 

Highlights

• •Low MDSC in peripheral blood correlate with response to chemo-immunotherapy.
• •Increased antigen specific T cells recognizing IGF-1R correlate with responses.
• •There was no advantage in overall survival with this combination compared to nab-paclitaxel alone.

Background

Granulocyte 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.

Methods

Recurrent 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.

Results

Twenty-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.

Conclusions

Nab-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.