Basal cell carcinoma: Management of advanced or metastatic cancer with checkpoint inhibitors and concurrent paradoxical development of new superficial tumors
2020; Elsevier BV; Volume: 82; Issue: 6 Linguagem: Inglês
10.1016/j.jaad.2020.02.052
ISSN1097-6787
AutoresPhilip R Cohen, Razelle Kurzrock,
Tópico(s)Cancer and Skin Lesions
ResumoTo the Editor: Choi et al1Choi F.D. Kraus C.N. Elsensohn A.N. et al.Programmed cell death 1 protein and programmed death-ligand 1 inhibitors in the treatment of nonmelanoma skin cancers: a systematic review.J Am Acad Dermatol. 2020; 82: 440-459Abstract Full Text Full Text PDF PubMed Scopus (31) Google Scholar provided a comprehensive review of programmed cell death 1 protein (PD-1) and programmed death ligand 1 (PD-L1) inhibitors in the treatment of nonmelanoma skin cancer. However, they incorrectly commented that the new primary cutaneous superficial basal cell carcinomas (BCCs) that paradoxically developed in our patient with metastatic BCC also responded to nivolumab.2Ikeda S. Goodman A.M. Cohen P.R. et al.Metastatic basal cell carcinoma with amplification of PD-L1: exceptional response to anti-PD1 therapy.NPJ Genom Med. 2016; 1: 16037Crossref PubMed Scopus (96) Google Scholar, 3Cohen P.R. Kato S. Goodman A.M. Ikeda S. Kurzrock R. Appearance of new cutaneous superficial basal cell carcinomas during successful nivolumab treatment of refractory metastatic disease: implications for immunotherapy in early versus late disease.Int J Mol Sci. 2017; 18: E1663Crossref PubMed Scopus (28) Google Scholar, 4Goodman A.M. Kato S. Cohen P.R. et al.Genomic landscape of advanced basal cell carcinoma: implications for precision treatment with targeted and immune therapies.Oncoimmunology. 2017; 7: e1404217Crossref PubMed Scopus (34) Google Scholar We want to emphasize this important observation, because it provides additional insight into the mechanism of therapeutic benefit and limitations when immunotherapy is considered for patients with metastatic BCC, and to share the experience of additional patients with advanced or metastatic BCC who were treated with checkpoint inhibitors.4Goodman A.M. Kato S. Cohen P.R. et al.Genomic landscape of advanced basal cell carcinoma: implications for precision treatment with targeted and immune therapies.Oncoimmunology. 2017; 7: e1404217Crossref PubMed Scopus (34) Google Scholar,5Nikanjam M. Cohen P.R. Kato S. Sicklick J.K. Kurzrock R. Advanced basal cell cancer: concise review of molecular characteristics and novel targeted and immune therapeutics.Ann Oncol. 2018; 29: 2192-2199Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar The first patient, a 58-year-old man, developed new primary cutaneous BCCs 9 months after nivolumab was initiated and achieved near complete remission of his widely metastatic BCC. His metastatic tumor had been refractory to treatment with chemotherapy (cisplatin and paclitaxel) and Hedgehog pathway inhibitors (vismodegib and sonidegib; the latter was combined with buparlisib, a pan-class I PI3K [phosphatiduylinositol 3-kinase] inhibitor). Next-generation sequencing (NGS) of his liver metastasis showed not only multiple genomic alterations (including PD-L1 amplification) but also a tumor mutational burden (TMB) of 103 mutations per megabase (m/mb); 20 m/mb or greater is considered to be a high TMB and is associated with better responses to immunotherapy. In contrast, the new primary cutaneous BCCs had fewer genomic alterations, did not exhibit PD-L1 amplification, and had a lower TMB of 45 m/mb.2Ikeda S. Goodman A.M. Cohen P.R. et al.Metastatic basal cell carcinoma with amplification of PD-L1: exceptional response to anti-PD1 therapy.NPJ Genom Med. 2016; 1: 16037Crossref PubMed Scopus (96) Google Scholar, 3Cohen P.R. Kato S. Goodman A.M. Ikeda S. Kurzrock R. Appearance of new cutaneous superficial basal cell carcinomas during successful nivolumab treatment of refractory metastatic disease: implications for immunotherapy in early versus late disease.Int J Mol Sci. 2017; 18: E1663Crossref PubMed Scopus (28) Google Scholar, 4Goodman A.M. Kato S. Cohen P.R. et al.Genomic landscape of advanced basal cell carcinoma: implications for precision treatment with targeted and immune therapies.Oncoimmunology. 2017; 7: e1404217Crossref PubMed Scopus (34) Google Scholar,6Cohen P.R. Basal cell carcinoma: additional subtypes and therapeutic advances.J Am Acad Dermatol. 2019; 81: e17Abstract Full Text Full Text PDF PubMed Scopus (4) Google Scholar The second patient, a 62-year-old man, presented with an advanced BCC on his upper back (Fig 1, A). NGS of his tumor showed 11 significant genomic variants and a high TMB (53 m/mb). He was treated with vismodegib and nivolumab and achieved complete remission after 5 months of treatment. Vismodegib was stopped after 8.5 months. This patient continues to remain in remission more than 12 months after stopping therapy (Fig 1, B).4Goodman A.M. Kato S. Cohen P.R. et al.Genomic landscape of advanced basal cell carcinoma: implications for precision treatment with targeted and immune therapies.Oncoimmunology. 2017; 7: e1404217Crossref PubMed Scopus (34) Google Scholar,5Nikanjam M. Cohen P.R. Kato S. Sicklick J.K. Kurzrock R. Advanced basal cell cancer: concise review of molecular characteristics and novel targeted and immune therapeutics.Ann Oncol. 2018; 29: 2192-2199Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar The third patient, a 53-year-old woman, had metastatic BCC. NGS of her cutaneous and metastatic tumor showed 6 and 12 genomic alterations, respectively; both tumors had a high TMB (90 m/mb). She achieved partial remission with vismodegib and, subsequently, nivolumab; however, her progression-free survival was only 4.5 months and 3.8 months, respectively.4Goodman A.M. Kato S. Cohen P.R. et al.Genomic landscape of advanced basal cell carcinoma: implications for precision treatment with targeted and immune therapies.Oncoimmunology. 2017; 7: e1404217Crossref PubMed Scopus (34) Google Scholar The fourth patient, a 50-year-old woman, had metastatic BCC; NGS showed 10 genomic alterations and a TMB of 102 m/mb. Vismodegib resulted in a partial remission lasting 11.1 months; progressive disease occurred 2.5 months after starting pembrolizumab.4Goodman A.M. Kato S. Cohen P.R. et al.Genomic landscape of advanced basal cell carcinoma: implications for precision treatment with targeted and immune therapies.Oncoimmunology. 2017; 7: e1404217Crossref PubMed Scopus (34) Google Scholar In summary, we propose that checkpoint inhibitors may be more successful in patients with late metastatic disease in which the tumor has more genomic aberrations and high TMB. In contrast, treatment with targeted therapies such as vismodegib (or excision for localized disease) may be better for patients with genomically less complex BCCs. In our patient, the paradoxical development of new superficial cutaneous BCC—in the setting of concurrently receiving immunotherapy and achieving near complete remission of his metastatic BCC—occurred because the checkpoint inhibitor was not able to prevent his early neoplastic disease, which was characterized by fewer molecular alterations and a lower TMB. Programmed cell death 1 protein and programmed death-ligand 1 inhibitors in the treatment of nonmelanoma skin cancer: A systematic reviewJournal of the American Academy of DermatologyVol. 82Issue 2PreviewImmunotherapy using programmed cell death 1 protein (PD-1) or programmed death-ligand 1 (PD-L1) inhibitors has been increasingly reported in a variety of nonmelanoma skin cancers (NMSCs). Full-Text PDF Reply to Letter to the Editor regarding: "Basal cell carcinoma: Management of advanced or metastatic cancer with checkpoint inhibitors and concurrent paradoxical development of new superficial tumors"Journal of the American Academy of DermatologyVol. 86Issue 3PreviewTo the Editor: We read the Cohen et al1 paper, "Basal cell carcinoma: Management of advanced or metastatic cancer with checkpoint inhibitors and concurrent paradoxical development of new superficial tumors" with interest. Full-Text PDF
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