Alopecia Incidence Characterised for Molecularly Targeted Cancer Treatments

The incidence of alopecia in patients given molecularly targeted cancer therapy varies between agents

medwireNews: A review and meta-analysis highlights the incidence of alopecia among oncology patients treated with molecularly targeted agents, suggesting a significantly higher overall rate of the adverse event than with placebo, albeit lower than that seen with chemotherapy.

“With the expanding indications for targeted agents (including off-label use), there is an urgent need for prospective studies and investigation into the mechanistic basis of this distressing condition (alopecia), and design of evidence-based management strategies” write Mario Lacouture, from Memorial Sloan Kettering Cancer Center in New York, USA, and team.

“This is also crucial to direct supportive care efforts, ensure consistent dosing, treatment compliance and maintain patients’ [health-related quality of life].”

The overall incidence of all-grade alopecia was 14.7% in the participants of 119 phase II or III clinical trials of agents targeting 18 different pathways and molecules, the majority of which were used in patients with solid tumours.

But the incidence varied significantly between agents, with the highest rates of all-cause alopecia reported for the SMO inhibitor vismodegib (56.9%), the VEGFR inhibitors sorafenib (29.0%) and regorafenib (23.5%), and the BRAF inhibitors vemurafenib (23.7%) and dabrafenib (18.9%).

And analysis of individual trial drugs gave an all-cause alopecia incidence of between 0.25% in a phase III trial of the EGFR inhibitor erlotinib in non-small-cell lung cancer patients and 80.0% for a phase II trial of sorafenib against medullary thyroid cancer.

Data from 15 randomised controlled trials comparing the tyrosine kinase inhibitors cabozantinib, pazopanib or sunitinib , and regorafenib, sorafenib or vismodegib against placebo showed all-grade alopecia occurred in 20.9% of the patients given the molecularly targeted agents compared with 2.8% of controls, giving a significant relative risk of 7.9.

Meanwhile, meta-analysis of 13 randomised controlled trials to compare the incidence of all-grade alopecia in patients given molecularly targeted agents versus chemotherapy revealed significant heterogeneity but the adverse event was identified in 6.1% versus 17.0%, giving an overall significant relative risk of 0.32.

Writing in the Annals of Oncology, the researchers observe that the mechanisms behind alopecia in patients given molecularly targeted agents are “poorly understood”, noting that the rate of alopecia even differs between agents targeting the same molecular target.

“However, it must be acknowledged that each of these drugs often target multiple other pathways (e.g. Raf, FGFR, PDGFR, c-MET, c-KIT), and besides, the spectrum of inhibition and receptor affinity might vary”, they emphasise.

“This suggests that various pathogenic mechanisms may be involved.”


Belum VR, Marulanda K, Ensslin C, et al. Alopecia in patients treated with molecularly targeted anticancer therapies. Ann Oncol 2015; Advance online publication 19 September. doi: 10.1093/annonc/mdv390

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