Azam Faruque, Vazquez Alexei
Wolfson Wohl Cancer Research Centre, Institute of Cancer Sciences, University of Glasgow, Garscube Estate, Switchback Road, Bearsden, Glasgow G61 1QH, UK.
Cancer Research UK Beatson Institute, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
Cancers (Basel). 2021 Jan 7;13(2):178. doi: 10.3390/cancers13020178.
: Drug combinations are the standard of care in cancer treatment. Identifying effective cancer drug combinations has become more challenging because of the increasing number of drugs. However, a substantial number of cancer drugs stumble at Phase III clinical trials despite exhibiting favourable efficacy in the earlier Phase. : We analysed recent Phase II cancer trials comprising 2165 response rates to uncover trends in cancer therapies and used a null model of non-interacting agents to infer synergistic and antagonistic drug combinations. We compared our latest efficacy dataset with a previous dataset to assess the progress of cancer therapy. : Targeted therapies reach higher response rates when used in combination with cytotoxic drugs. We identify four synergistic and 10 antagonistic combinations based on the observed and expected response rates. We demonstrate that recent targeted agents have not significantly increased the response rates. : We conclude that either we are not making progress or response rate measured by tumour shrinkage is not a reliable surrogate endpoint for the targeted agents.
药物联合是癌症治疗的标准治疗方法。由于药物数量不断增加，确定有效的癌症药物联合方案变得更具挑战性。然而，尽管许多癌症药物在早期阶段显示出良好的疗效，但在III期临床试验中却遭遇挫折。：我们分析了近期包含2165个缓解率的II期癌症试验，以揭示癌症治疗的趋势，并使用非相互作用药物的零模型来推断协同和拮抗药物联合方案。我们将最新的疗效数据集与之前的数据集进行比较，以评估癌症治疗的进展。：靶向治疗与细胞毒性药物联合使用时可达到更高的缓解率。基于观察到的和预期的缓解率，我们确定了4种协同组合和10种拮抗组合。我们证明，近期的靶向药物并未显著提高缓解率。：我们得出结论，要么我们没有取得进展，要么通过肿瘤缩小测量的缓解率不是靶向药物可靠的替代终点。
