An FDA analysis of the association of tumor growth rate, overall survival, and progression-free survival in patients with metastatic non-small cell lung cancer

BACKGROUND: Despite recent advances and an improved treatment paradigm, the prognosis in patients with advanced non-small-cell lung cancer (NSCLC) remains poor. Novel endpoints to evaluate antitumor activity are needed to expedite safe and effective drug development. METHODS: We performed a retrospective pooled analysis of 10,495 patients with NSCLC using radiological tumor measurements across 22 randomized clinical trials fit to a regression-growth model to derive the g value. We evaluated the g value across both type and line of therapy. RESULTS: The g value is inversely associated with survival. Patients receiving targeted therapy had lower g values than patients receiving immune checkpoint inhibitors or chemotherapy. Additionally, patients receiving front-line treatment had a lower g value than patients receiving later line treatment. A lower g value was associated with a higher median overall survival (OS) and a longer median progression-free survival (PFS). CONCLUSION: The g value, as a volumetric measurement of tumor growth rate, may provide an additional or supplementary approach to assess the potential clinical activity of an agent. Prospective studies are needed to further assess the association of the g value derived from early tumor measurements with long-term outcomes in patients.