International Journal of Clinical Pharmacy

, Volume 40, Issue 4, pp 852–861 | Cite as

Using a cancer registry to capture signals of adverse events following immune and targeted therapy for melanoma

  • João P. Aguiar
  • Fábio Cardoso Borges
  • Rodrigo Murteira
  • Catarina Ramos
  • Emanuel Gouveia
  • Maria José Passos
  • Ana Miranda
  • Filipa Alves da CostaEmail author
Research Article

Background Toxicity of oncology treatments in real-life patients is frequently disregarded and hence underreported. Objective To characterize adverse events (AEs) of immunotherapy and targeted therapy reported in patients with locally advanced or metastatic melanoma. Setting District Hospital for Cancer treatment (Instituto Português de Oncologia de Lisboa Francisco Gentil). Method A retrospective cohort of melanoma patients was established, comprising adult patients diagnosed with malignant melanoma treated with immunotherapy or targeted therapy. Exposure was characterized by nature, time and intensity of exposure. To account for different exposure periods, person-time was used as unit of analysis. Main outcomes measure Occurrence of AEs. Results Data from 111 patients included in the cohort indicates the majority received immunotherapy regimens (CTLA-4, anti-PD-1 and combination therapy; (n = 70; 63.1%), among which anti-PD-1 were the predominant treatment. Pembrolizumab was the most frequently prescribed drug (n = 30; 45.7%). Three hundred and seventy-one AEs were extracted. The incidence of AEs was lower in the anti-PD-1 mAc group (54 AEs per 1000 person.months) and the number of AEs/patient was also lower (3.1 ± 2.0). Grade 3 to 4 AEs occurred in 15.3% (n = 17) of the cohort, being more common in the targeted therapy group. Forty-two (11.6%) of the extracted AEs were not described in the Summary of Product Characteristics of the drugs under study. Conclusion This study suggests various known and unknown AEs of immunotherapy and targeted therapy may be identified using the Cancer Registry database. These events should be considered as signals worth further investigation for assessment of causality as the underreporting of AEs in cancer may have potential implications for the patient’s quality of life.


Adverse drug reactions Adverse events Drug-related side effects and adverse reactions Immunotherapy Malignant melanoma Pharmacovigilance 



The authors would like to acknowledge the oncologists of IPO-Lisboa for the quality information registered in medical records.


This study received no specific funding.

Conflicts of interest

The authors declare they have no conflicts of interest.


  1. 1.
    Lucas R, McMichael T, Smith W, Armstrong B. Solar ultraviolet radiation: global burden of disease from solar ultraviolet radiation. Environ Burd Dis Ser. 2006;55(13):987–99.Google Scholar
  2. 2.
    World Health Organization (WHO). Skin cancers. Accessed 11 Mar 2017.
  3. 3.
    European Cancer Observatory. EUCAN Factsheets: Malignant Melanoma of Skin [Internet]. Cancer Factsheets. 2012 [cited 2017 Dec 17].
  4. 4.
    Ribas A, Gonzalez R, Pavlick A, Hamid O, Gajewski TF, Daud A, et al. Combination of vemurafenib and cobimetinib in patients with advanced BRAFV600-mutated melanoma: a phase 1b study. Lancet Oncol. 2014;15(9):954–65.CrossRefPubMedGoogle Scholar
  5. 5.
    Hauschild A, Grob JJ, Demidov LV, Jouary T, Gutzmer R, Millward M, et al. Dabrafenib in BRAF-mutated metastatic melanoma: a multicentre, open-label, phase 3 randomised controlled trial. Lancet. 2012;380(9839):358–65.CrossRefPubMedGoogle Scholar
  6. 6.
    Ugurel S, Röhmel J, Ascierto PA, Flaherty KT, Grob JJ, Hauschild A, et al. Survival of patients with advanced metastatic melanoma: the impact of novel therapies. Eur J Cancer. 2016;53:125–34.CrossRefPubMedGoogle Scholar
  7. 7.
    World Health Organization. International Classification of Diseases for Oncology (ICD-O)—3rd edition 1st revision. WHO Library Cataloguing-in-Publication Data. 2013.Google Scholar
  8. 8.
    Edge SB, Compton CC. The American Joint Committee on Cancer: the 7th edition of the AJCC cancer staging manual and the future of TNM. Ann Surg Oncol. 2010;17(6):1471–4.CrossRefPubMedGoogle Scholar
  9. 9.
    Guideline on good pharmacovigilance practices (GVP)—Annex I (Rev 2) EMA/876333/2011 Rev 2 (superseded version) available at Assessed 5th May 2018.

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.iMED.ULisboa – Research Institute for Medicines, Faculdade de FarmáciaUniversidade de LisboaLisbonPortugal
  2. 2.Registo Oncológico Regional Sul (ROR-Sul)Instituto Português de Oncologia de Lisboa Francisco GentilLisbonPortugal
  3. 3.Serviço de Oncologia MédicaInstituto Português de Oncologia de Lisboa Francisco GentilLisbonPortugal
  4. 4.Centro de Investigação Interdisciplinar Egas Moniz (CiiEM)CaparicaPortugal

Personalised recommendations