Combination therapy with IGF-1R antibodies and mTOR inhibitors significantly improved progression-free survival compared to IGF-1R antibodies alone in Ewing sarcoma (3.3 vs 1.6 months, p=0.042).
Meta-Analysis (n=56)
Yes
Does the combination of IGF-1R antibodies and mTOR inhibitors improve progression-free survival compared to IGF-1R antibodies alone in Ewing sarcoma patients?
The combination of IGF-1R antibodies and mTOR inhibitors significantly improves progression-free survival in Ewing sarcoma patients compared to IGF-1R antibodies alone, with low pIGF-1R and reduced total-lesion glycolysis serving as potential predictive biomarkers.
Absolute Event Rate: 3.3% vs 1.6%
p-value: p=0.042
Background : Ten to fourteen percent of Ewing sarcoma (ES) study participants treated nationwide with IGF-1 receptor (IGF-1R)-targeted antibodies achieved tumor regression. Despite this success, low response rates and short response durations (approximately 7-weeks) have slowed the development of this therapy. Methods: We performed a meta-analysis of five phase-1b/2 ES-oriented trials that evaluated the anticancer activity of IGF-1R antibodies +/− mTOR inhibitors (mTORi). Our meta-analysis provided a head-to-head comparison of the clinical benefits of IGF-1R antibodies vs. the IGF-1R/mTOR-targeted combination. Available pretreatment clinical samples were semi-quantitatively scored using immunohistochemistry to detect proteins in the IGF-1R/PI3K/AKT/mTOR pathway linked to clinical response. Early PET/CT imaging, obtained within the first 2 weeks (median 10 days), were examined to determine if reduced FDG avidity was predictive of progression-free survival (PFS). Results: Among 56 ES patients treated at MD Anderson Cancer Center (MDACC) with IGF-1R antibodies, our analysis revealed a significant ~two-fold improvement in PFS that favored a combination of IGF-1R/mTORi therapy (1.6 vs. 3.3-months, p = 0.042). Low pIGF-1R in the pretreatment specimens was associated with treatment response. Reduced total-lesion glycolysis more accurately predicted the IGF-1R response than other previously reported radiological biomarkers. Conclusion: Synergistic drug combinations, and newly identified proteomic or radiological biomarkers of IGF-1R response, may be incorporated into future IGF-1R-related trials to improve the response rate in ES patients.
Amin et al. (Thu,) conducted a meta-analysis in Ewing sarcoma (n=56). IGF-1R antibodies + mTOR inhibitors vs. IGF-1R antibodies alone was evaluated on Progression-free survival (PFS) (p=0.042). Combination therapy with IGF-1R antibodies and mTOR inhibitors significantly improved progression-free survival compared to IGF-1R antibodies alone in Ewing sarcoma (3.3 vs 1.6 months, p=0.042).
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