This 2021 narrative review by Gill and Gorlick surveys the treatment landscape of osteosarcoma — the most common primary bone malignancy in children and young adults. It asks why survival has stagnated for four decades and what molecular, immunologic, and clinical trial innovations may finally change outcomes. The review covers current MAP chemotherapy, molecular subclassification, preclinical models, targeted agents, and immune-based strategies.
A young patient with osteosarcoma progressing through MAP chemotherapy faces a median EFS of 4 months and a 2-year EFS of 12% — numbers that have been unchanged across decades of phase II trials.
Those numbers are not just prognostic. They are the foundation of how new agents are tested in this disease. When you see a trial offering enrollment to a relapsed osteosarcoma patient, know that the 40% disease control rate at 4 months threshold is what separates an active agent from noise in this population.
For the management of refractory disease, single-agent checkpoint inhibition is not a rational choice. Pembrolizumab and nivolumab have both failed convincingly. The active investigational paths are ADCs targeting B7-H3, GPNMB, or LRRC15 (expressed in >91% of tumors), or CAR T cell strategies, particularly for HER2-positive disease where early CR data exist.
The authors note that novel agents will likely need non-overlapping toxicity profiles to be safely combined with the high-dose cytotoxic regimens currently used. This is why TKIs are being explored as maintenance therapy rather than concurrent additions to MAP.
This 2021 narrative review by Gill and Gorlick surveys the treatment landscape of osteosarcoma — the most common primary bone malignancy in children and young adults. It asks why survival has stagnated for four decades and what molecular, immunologic, and clinical trial innovations may finally change outcomes. The review covers current MAP chemotherapy, molecular subclassification, preclinical models, targeted agents, and immune-based strategies.
A young patient with osteosarcoma progressing through MAP chemotherapy faces a median EFS of 4 months and a 2-year EFS of 12% — numbers that have been unchanged across decades of phase II trials.
Those numbers are not just prognostic. They are the foundation of how new agents are tested in this disease. When you see a trial offering enrollment to a relapsed osteosarcoma patient, know that the 40% disease control rate at 4 months threshold is what separates an active agent from noise in this population.
For the management of refractory disease, single-agent checkpoint inhibition is not a rational choice. Pembrolizumab and nivolumab have both failed convincingly. The active investigational paths are ADCs targeting B7-H3, GPNMB, or LRRC15 (expressed in >91% of tumors), or CAR T cell strategies, particularly for HER2-positive disease where early CR data exist.
The authors note that novel agents will likely need non-overlapping toxicity profiles to be safely combined with the high-dose cytotoxic regimens currently used. This is why TKIs are being explored as maintenance therapy rather than concurrent additions to MAP.