The cancer treatment landscape has changed dramatically since the turn of the century, resulting in substantial improvements in outcomes for patients. This Review summarizes trends in the approval of ...oncology therapeutic products by the United States Food and Drug Administration (FDA) from January 2000 to October 2022, based on a categorization of these products by their mechanism of action and primary target. Notably, the rate of oncology indication approvals has increased in this time, driven by approvals for targeted therapies, as has the rate of introduction of new therapeutic approaches. Kinase inhibitors are the dominant product class by number of approved products and indications, yet immune checkpoint inhibitors have the second most approvals despite not entering the market until 2011. Other trends include a slight increase in the share of approvals for biomarker-defined populations and the emergence of tumour-site-agnostic approvals. Finally, we consider the implications of the trends for the future of oncology therapeutic product development, including the impact of novel therapeutic approaches and technologies.
Abstract On October 29, 2021, FDA granted accelerated approval to asciminib (SCEMBLIX; Novartis), a tyrosine kinase inhibitor (TKI), for the treatment of adult patients with Philadelphia chromosome ...positive chronic myeloid leukemia (Ph+ CML) in chronic phase (CP), previously treated with two or more TKIs, and granted traditional approval to asciminib for adult patients with Ph+ CML in CP with the T315I mutation. The first indication was approved based on major molecular response (MMR) at 24 weeks in the ASCEMBL study, a randomized trial comparing asciminib with bosutinib in patients who had failed two or more TKIs. This indication was ultimately granted traditional approval on October 12, 2022, based on safety data and MMR rate at 96 weeks of 38% 95% confidence interval (CI), 30–46 in the asciminib arm versus 16% (95% CI, 8–26) in the bosutinib arm (P value: 0.001). The second indication was approved based on MMR rate by 96 weeks of 49% (95% CI, 34–64) in the single-arm CABL001X2101 study. The most common (≥20%) adverse reactions included upper respiratory tract infections, musculoskeletal pain, headache, fatigue, nausea, rash, and diarrhea. The most common (≥20%) laboratory abnormalities were thrombocytopenia, neutropenia, anemia, lymphopenia, hypertriglyceridemia, hyperuricemia, and increases in creatine kinase, alanine aminotransferase, aspartate aminotransferase, lipase, and amylase. This manuscript describes the basis for approval of these indications.
In 2022, cancer drug development continued to progress rapidly despite the lingering COVID-19 pandemic. Highlights of U.S. drug approvals for oncology indications this year include ongoing ...development in rare diseases and molecular subgroups, improved dosage optimization, and updated data for drugs granted accelerated approval, with confirmatory studies demonstrating verification of clinical benefit in some instances, as well as indication withdrawal when clinical benefit was not verified.
The FDA has an accelerated approval program for drugs that have been identified as promising treatments for serious conditions when the available data suggest that the benefits outweigh the ...foreseeable risks. All of the currently available treatment options for chronic myeloid leukemia (CML) initially went through the accelerated approval program. Here, a group of academic CML experts, patient panelists, and members from the FDA convened to discuss the utility of the accelerated approval program as it pertains to CML, and the utility of this program in future drug development in this disease. The results of that discussion are summarized here.
Cancer drug development remained robust in 2023. Highlights of U.S. drug approvals this year include new immunotherapies and targeted drug development in adult and pediatric patients as well as ...patients with rare diseases.
Treatment with tyrosine kinase inhibitors (TKIs) has dramatically changed the life expectancy of chronic myeloid leukaemia (CML) patients. Although the impact of first‐generation TKIs on quality of ...life (QoL) was shown in CML, the effects of new generic formulations of imatinib mesylate (IM) are unclear. We evaluated differences in QoL under treatment with first‐ or second‐generation TKIs. Fifty‐two patients diagnosed with CP‐CML completed the European Organization for Research and Treatment of Cancer Quality of Life Questionaire‐C30, Hospital Anxiety and Depression Scale, and General Health Questionnaire. General QoL scores were similar between groups. There was a significant difference in the frequency of diarrhoea between IM group and the group using new generic formulations of IM (P = 0.012). General QoL score tended to be higher in patients with disease duration longer than 3 years (P = 0.052). GHQ, anxiety and depression scores correlated positively with symptom scales and negatively with functional subscales.CML patients using new generic formulations of IM reported a higher frequency of diarrhoea than patients using original IM and second‐generation TKIs that could result in more drug discontinuation.
Treatment with tyrosine kinase inhibitors (TKIs) has dramatically changed the life expectancy of chronic myeloid leukaemia (CML) patients. Although the impact of first-generation TKIs on quality of ...life (QoL) was shown in CML, the effects of new generic formulations of imatinib mesylate (IM) are unclear. We evaluated differences in QoL under treatment with first- or second-generation TKIs. Fifty-two patients diagnosed with CP-CML completed the European Organization for Research and Treatment of Cancer Quality of Life Questionaire-C30, Hospital Anxiety and Depression Scale, and General Health Questionnaire. General QoL scores were similar between groups. There was a significant difference in the frequency of diarrhoea between IM group and the group using new generic formulations of IM (P = 0.012). General QoL score tended to be higher in patients with disease duration longer than 3 years (P = 0.052). GHQ, anxiety and depression scores correlated positively with symptom scales and negatively with functional subscales.CML patients using new generic formulations of IM reported a higher frequency of diarrhoea than patients using original IM and second-generation TKIs that could result in more drug discontinuation. MEDIUM References
