Cancer patients may have less tolerance for targeted therapies and checkpoint inhibitors when they are used in adjuvant settings rather than metastatic settings, new research suggests.
A review of 29 oncology drugs clinical trials found that discontinuation rates due to intolerance for the same drug were sometimes almost double among patients in the adjuvant setting than in the metastatic setting, even though absolute rates of adverse effects were similar.
The review covered trials of drugs used for breast cancer (31%) melanoma and non–small cell lung cancer (17%), urothelial cancer (10%) and small cell lung cancer (7%) as well as several other less common cancers. About a quarter 24% of cytotoxic drugs and checkpoint inhibitors and half the targeted drug types (52%) were used in the adjuvant setting.
The overall discontinuation rate because of adverse events or patient withdrawal was 21.4% for patients treated in the adjuvant setting compared with a median of 15.9% in the metastatic setting (P = 0.01).
Checkpoint inhibitors showed a significantly higher rate of discontinuation in adjuvant settings compared to metastatic settings ( 21.4% vs 15.2%, P = 0.01), as did targeted drugs (27.7% vs 14.0%; P < 0.001). However, cytotoxic drugs (median rate of discontinuation, 16.6% vs 25.5%, P = 0.07) showed no difference between the two settings.
The largest differences between adjuvant and metastatic discontinuation rates were for sorafenib (renal cell carcinoma, 43.8% vs 5.5%), imatinib (GI stromal tumour, 37.4% vs 6.1%) and erlotinib (NSCLC, 37.5% vs 8.4%).
The study authors from City University New York, said the disparity in discontinuation rates supported the hypothesis that a patient’s tolerance for oncology therapies may differ in the adjuvant setting, in which drugs are administered for primarily noncurative purposes, in contrast to the metastatic, where the intent of treatment is to prevent the spread of the tumour.