Tom 7, Nr 5 (2021)
Artykuł przeglądowy
Opublikowany online: 2021-11-25
Wyświetlenia strony
3246
Wyświetlenia/pobrania artykułu
251
Immunoterapia w leczeniu chorych na niebarwnikowe nowotwory skóry
Onkol Prakt Klin Edu 2021;7(5):319-330.
Streszczenie
Raki skóry to najczęstsze nowotwory złośliwe. Ryzyko zachorowania wzrasta wraz z wiekiem i w ciągu całego życia jest duże. Postaci zaawansowane miejscowo, niekwalifikujące się do zabiegowego leczenia miejscowego i radioterapii, stwierdzane są stosunkowo rzadko, ale w związku z ich częstą lokalizacją w odsłoniętych okolicach ciała (w szczególności na twarzy) oraz u często obciążonych schorzeniami współistniejącymi osób w starszym wieku, ich leczenie stanowi szczególne wyzwanie. Jeszcze niedawno brak było skutecznych metod leczenia systemowego tych nowotworów, w przypadku braku możliwości leczenia miejscowego. Od niecałych 10 lat w leczeniu raka podstawnokomórkowego dostępne są leki ukierunkowane molekularnie — inhibitory szlaku Hedgehog. Od tego czasu przeprowadzono liczne badania kliniczne, które udowodniły skuteczność immunoterapii w leczeniu niebarwnikowych nowotworów skóry, w tym raka podstawnokomórkowgo, raka kolczystokomórkowego oraz raka z komórek Merkla. W poniższej pracy przedstawiono wyniki najważniejszych badań klinicznych z zastosowaniem immunoterapii w niebarwnikowych nowotworach złośliwych skóry, zarejestowane wskazania i aktualne możliwości refundacyjne w Polsce a także perspektywy immunoterapii w tych wskazaniach.
Słowa kluczowe: rak podstawnokomórkowyrak kolczystokomórkowyrak z komórek MerklawismodegibcemiplimabawelumabpembrolizumabBCCCSCCMCCinhibitor PD-L1inhibitor PD-1
Referencje
- Lomas A, Leonardi-Bee J, Bath-Hextall F. A systematic review of worldwide incidence of nonmelanoma skin cancer. Br J Dermatol. 2012; 166(5): 1069–1080.
- Rogers HW, Weinstock MA, Feldman SR, et al. Incidence Estimate of Nonmelanoma Skin Cancer (Keratinocyte Carcinomas) in the U.S. Population, 2012. JAMA Dermatol. 2015; 151(10): 1081–1086.
- Rutkowski P, Owczarek W, Nejc D, et al. Raki skóry. Onkol Prakt Klin Edu. 2020; 6(4): 203–224.
- Squamous Cell Skin Cancer. NCCN guidelines. V. 1 2021.
- Merkel Cell Carcinoma. NCCN Guidelines. V. 1 2021.
- Chan TA, Yarchoan M, Jaffee E, et al. Development of tumor mutation burden as an immunotherapy biomarker: utility for the oncology clinic. Ann Oncol. 2019; 30(1): 44–56.
- Winkler JK, Schneiderbauer R, Bender C, et al. Anti-programmed cell death-1 therapy in nonmelanoma skin cancer. Br J Dermatol. 2017; 176(2): 498–502.
- Ikeda S, Goodman AM, Cohen PR, et al. Metastatic basal cell carcinoma with amplification of PD-L1: exceptional response to anti-PD1 therapy. NPJ Genom Med. 2016; 1.
- Mohan SV, Kuo KY, Chang AL. Incidental regression of an advanced basal cell carcinoma after ipilimumab exposure for metastatic melanoma. JAAD Case Rep. 2016; 2(1): 13–15.
- Falchook GS, Leidner R, Stankevich E, et al. Responses of metastatic basal cell and cutaneous squamous cell carcinomas to anti-PD1 monoclonal antibody REGN2810. J Immunother Cancer. 2016; 4: 70.
- Borradori L, Sutton B, Shayesteh P, et al. Rescue therapy with anti-programmed cell death protein 1 inhibitors of advanced cutaneous squamous cell carcinoma and basosquamous carcinoma: preliminary experience in five cases. Br J Dermatol. 2016; 175(6): 1382–1386.
- Lipson EJ, Lilo MT, Ogurtsova A, et al. Basal cell carcinoma: PD-L1/PD-1 checkpoint expression and tumor regression after PD-1 blockade. J Immunother Cancer. 2017; 5: 23.
- Burova E, Hermann A, Waite J, et al. Characterization of the Anti-PD-1 Antibody REGN2810 and Its Antitumor Activity in Human Knock-In Mice. Mol Cancer Ther. 2017; 16(5): 861–870.
- Libtayo, cemiplimab, Charakterystyka produktu leczniczego. https://www.ema.europa.eu/en/documents/product-information/libtayo-epar-product-information_pl.pdf.
- Stratigos AJ, Sekulic A, Peris K, et al. LBA47 Primary analysis of phase II results for cemiplimab in patients (pts) with locally advanced basal cell carcinoma (laBCC) who progress on or are intolerant to hedgehog inhibitors (HHIs). Ann Oncol. 2020; 31: S1175–S1176.
- Lewis K, Peris K, Sekulic A, et al. 428 Interim analysis of Phase 2 results for cemiplimab in patients with metastatic basal cell carcinoma (mBCC) who progressed on or are intolerant to hedgehog inhibitors (HHIs). J Immunother Cancer. 2020; 8(Suppl 3): A453–A453.
- Stratigos AJ, Sekulic A, Peris K, et al. Cemiplimab in locally advanced basal cell carcinoma after hedgehog inhibitor therapy: an open-label, multi-centre, single-arm, phase 2 trial. Lancel Oncol. 2021; 22(6): 848–857.
- Libtayo (cemiplimab) prescribing information.
- Stratigos A, Chen CI, Ivanescu C, et al. Health-related quality of life (HRQoL) in patients (pts) with locally advanced basal cell carcinoma (laBCC) treated with cemiplimab: Analysis of a phase II, open-label clinical trial. Journal of Clinical Oncology. 2021; 39(15_suppl): 9566–9566.
- Papadopoulos K, Owonikoko T, Johnson M, et al. REGN2810: A fully human anti-PD-1 monoclonal antibody, for patients with unresectable locally advanced or metastatic cutaneous squamous cell carcinoma (CSCC)—Initial safety and efficacy from expansion cohorts (ECs) of phase I study. J Clin Oncol. 2017; 35(15_suppl): 9503–9503.
- Papadopoulos KP, Johnson ML, Lockhart AC, et al. First-In-Human Study of Cemiplimab Alone or In Combination with Radiotherapy and/or Low-dose Cyclophosphamide in Patients with Advanced Malignancies. Clin Cancer Res. 2020; 26(5): 1025–1033.
- Migden MR, Rischin D, Schmults CD, et al. PD-1 Blockade with Cemiplimab in Advanced Cutaneous Squamous-Cell Carcinoma. N Engl J Med. 2018; 379(4): 341–351.
- Falchook GS, Leidner R, Stankevich E, et al. Responses of metastatic basal cell and cutaneous squamous cell carcinomas to anti-PD1 monoclonal antibody REGN2810. J Immunother Cancer. 2016; 4: 70.
- Guminski A, Lim A, Khushalani N, et al. Phase 2 study of cemiplimab, a human monoclonal anti-PD-1, in patients (pts) with metastatic cutaneous squamous cell carcinoma (mCSCC; Group 1): 12-month follow-up. J Clin Oncol. 2019; 37(15_suppl): 9526–9526.
- Migden M, Khushalani N, Chang A, et al. Primary analysis of phase 2 results of cemiplimab, a human monoclonal anti-PD-1, in patients (pts) with locally advanced cutaneous squamous cell carcinoma (laCSCC). J Clin Oncol. 2019; 37(15_suppl): 6015–6015.
- Migden MR, Khushalani NI, Chang AL, et al. Cemiplimab in locally advanced cutaneous squamous cell carcinoma: results from an open-label, phase 2, single-arm trial. Lancet Oncol. 2020; 21(2): 294–305.
- Rischin D, Migden MR, Lim AM, et al. Phase 2 study of cemiplimab in patients with metastatic cutaneous squamous cell carcinoma: primary analysis of fixed-dosing, long-term outcome of weight-based dosing. J Immunother Cancer. 2020; 8(1).
- Migden M, Rischin D, Sasane M, et al. Health-related quality of life (HRQL) in patients with advanced cutaneous squamous cell carcinoma (CSCC) treated with cemiplimab: Post hoc exploratory analyses of a phase II clinical trial. J Clin Oncol. 2020; 38(15_suppl): 10033–10033.
- Rischin D, Khushalani N, Schmults C, et al. Phase II study of cemiplimab in patients (pts) with advanced cutaneous squamous cell carcinoma (CSCC): Longer follow-up. J Clin Oncol. 2020; 38(15_suppl): 10018–10018.
- Hober C, Fredeau L, Ledard A, et al. 1086P Cemiplimab for advanced cutaneous squamous cell carcinoma: Real life experience. Ann Oncol. 2020; 31: S737.
- Rabinowits G, Park S, Ellison D, et al. Checkpoint inhibition in immunosuppressed or immunocompromised patients with advanced cutaneous squamous cell carcinoma (CSCC): Data from prospective CemiplimAb-rwlc Survivorship and Epidemiology (C.A.S.E.) study. J Clin Oncol. 2021; 39(15_suppl): 9547–9547.
- Stevenson ML, Wang CQF, Abikhair M, et al. Expression of Programmed Cell Death Ligand in Cutaneous Squamous Cell Carcinoma and Treatment of Locally Advanced Disease With Pembrolizumab. JAMA Dermatol. 2017; 153(4): 299–303.
- Borradori L, Sutton B, Shayesteh P, et al. Rescue therapy with anti-programmed cell death protein 1 inhibitors of advanced cutaneous squamous cell carcinoma and basosquamous carcinoma: preliminary experience in five cases. Br J Dermatol. 2016; 175(6): 1382–1386.
- Tran DC, Colevas AD, Chang AL. Follow-up on Programmed Cell Death 1 Inhibitor for Cutaneous Squamous Cell Carcinoma. JAMA Dermatol. 2017; 153(1): 92–94.
- Blum V, Müller B, Hofer S, et al. Nivolumab for recurrent cutaneous squamous cell carcinoma: three cases. Eur J Dermatol. 2018; 28(1): 78–81.
- Chen A, Ali N, Boasberg P, et al. Clinical Remission of Cutaneous Squamous Cell Carcinoma of the Auricle with Cetuximab and Nivolumab. J Clin Med. 2018; 7(1).
- Choi FD, Kraus CN, Elsensohn AN, et al. Programmed cell death 1 protein and programmed death-ligand 1 inhibitors in the treatment of nonmelanoma skin cancer: A systematic review. J Am Acad Dermatol. 2020; 82(2): 440–459.
- Hughes BGM, Munoz-Couselo E, Mortier L, et al. Pembrolizumab for locally advanced and recurrent/metastatic cutaneous squamous cell carcinoma (KEYNOTE-629 Study): an open-label, nonrandomized, multicenter, phase 2 trial. Ann Oncol. 2021 [Epub ahead of print].
- Grob JJ, Gonzalez R, Basset-Seguin N, et al. Pembrolizumab Monotherapy for Recurrent or Metastatic Cutaneous Squamous Cell Carcinoma: A Single-Arm Phase II Trial (KEYNOTE-629). J Clin Oncol. 2020; 38(25): 2916–2925.
- Maubec E, Boubaya M, Petrow P, et al. Pembrolizumab as first line therapy in patients with unresectable squamous cell carcinoma of the skin: Interim results of the phase 2 CARSKIN trial. J Clin Oncol. 2018; 36(15_suppl): 9534–9534.
- Bavencio (awelumab), charakterystyka produktu leczniczego. https://www.ema.europa.eu/en/documents/product-information/bavencio-epar-product-information_pl.pdf.
- Kaufman HL, Russell J, Hamid O, et al. Avelumab in patients with chemotherapy-refractory metastatic Merkel cell carcinoma: a multicentre, single-group, open-label, phase 2 trial. Lancet Oncol. 2016; 17(10): 1374–1385.
- Nghiem P, Bhatia S, Brohl A, et al. Two-year efficacy and safety update from JAVELIN Merkel 200 part A: A registrational study of avelumab in metastatic Merkel cell carcinoma progressed on chemotherapy. J Clin Oncol. 2018; 36(15_suppl): 9507–9507.
- Kaufman HL, Russell JS, Hamid O, et al. Updated efficacy of avelumab in patients with previously treated metastatic Merkel cell carcinoma after ≥1 year of follow-up: JAVELIN Merkel 200, a phase 2 clinical trial. J Immunother Cancer. 2018; 6(1): 7.
- D'Angelo SP, Bhatia S, Brohl AS, et al. Avelumab in patients with previously treated metastatic Merkel cell carcinoma: long-term data and biomarker analyses from the single-arm phase 2 JAVELIN Merkel 200 trial. J Immunother Cancer. 2020; 8(1).
- Nghiem P, Bhatia S, Brohl A, et al. Avelumab in patients with previously treated Merkel cell carcinoma (JAVELIN Merkel 200): Updated overall survival data after more than five years of follow up. J Clin Oncol. 2021; 39(15_suppl): 9517–9517.
- Bullement A, D'Angelo S, Amin A, et al. Predicting overall survival in patients (pts) with treatment-naive metastatic Merkel cell carcinoma (mMCC) treated with avelumab. J Clin Oncol. 2018; 36(15_suppl): e21620–e21620.
- D'Angelo S, Russell J, Hassel J, et al. First-line (1L) avelumab treatment in patients (pts) with metastatic Merkel cell carcinoma (mMCC): Preliminary data from an ongoing study. J Clin Oncol. 2017; 35(15_suppl): 9530–9530.
- D'Angelo SP, Russell J, Lebbé C, et al. Efficacy and Safety of First-line Avelumab Treatment in Patients With Stage IV Metastatic Merkel Cell Carcinoma: A Preplanned Interim Analysis of a Clinical Trial. JAMA Oncol. 2018; 4(9): e180077.
- D'Angelo SP. First-line avelumab treatment in patients with metastatic Merkel cell carcinoma: primary analysis after ≥15 months of follow-up from JAVELIN Merkel 200, a registrational phase 2 trial. SITC. 2019: P362.
- Walker JW, Lebbé C, Grignani G, et al. Efficacy and safety of avelumab treatment in patients with metastatic Merkel cell carcinoma: experience from a global expanded access program. J Immunother Cancer. 2020; 8(1).
- Weppler A, Meda LDa, Silva I, et al. Durability of response to immune checkpoint inhibitors (ICI) in metastatic Merkel cell carcinoma (mMCC) after treatment cessation. J Clin Oncol. 2021; 39(15_suppl): 9543–9543.
- Nghiem PT, Bhatia S, Lipson EJ, et al. PD-1 Blockade with Pembrolizumab in Advanced Merkel-Cell Carcinoma. N Engl J Med. 2016; 374(26): 2542–2552.
- Nghiem P, Bhatia S, Lipson E, et al. Durable Tumor Regression and Overall Survival in Patients With Advanced Merkel Cell Carcinoma Receiving Pembrolizumab as First-Line Therapy. J Clin Oncol. 2019; 37(9): 693–702.
- Topalian S, Bhatia S, Hollebecque A, et al. Abstract CT074: Non-comparative, open-label, multiple cohort, phase 1/2 study to evaluate nivolumab (NIVO) in patients with virus-associated tumors (CheckMate 358): Efficacy and safety in Merkel cell carcinoma (MCC). Cancer Research. 2017; 77(supl_13): CT074.
- Chang AL, Tran DC, Cannon JGD, et al. Pembrolizumab for advanced basal cell carcinoma: An investigator-initiated, proof-of-concept study. J Am Acad Dermatol. 2019; 80(2): 564–566.
- Topalian SL, Bhatia S, Amin A, et al. Neoadjuvant Nivolumab for Patients With Resectable Merkel Cell Carcinoma in the CheckMate 358 Trial. J Clin Oncol. 2020; 38(22): 2476–2487.
- Topalian S, Bhatia S, Kudchadkar R, et al. Nivolumab (Nivo) as neoadjuvant therapy in patients with resectable Merkel cell carcinoma (MCC) in CheckMate 358. J Clin Oncol. 2018; 36(15_suppl): 9505–9505.
- Pembrolizumab Compared to Standard of Care Observation in Treating Patients With Completely Resected Stage I-III Merkel Cell Cancer, STAMP Study. https://clinicaltrials.gov/ct2/show/NCT03712605.
- Immunotherapy Adjuvant Trial in Patients With Stage I-III Merkel Cell Carcinoma (I-MAT). https://clinicaltrials.gov/ct2/show/NCT04291885.
- Adjuvant Avelumab in Merkel Cell Cancer (ADAM). https://clinicaltrials.gov/ct2/show/NCT03271372.
- Adjuvant Therapy of Completely Resected Merkel Cell Carcinoma With Immune Checkpoint Blocking Antibodies vs Observation (ADMEC-O). https://clinicaltrials.gov/ct2/show/NCT02196961.
- Grignani G, Burgess M, Depenni R, et al. POD1UM-201: A phase II study of retifanlimab (INCMGA00012) in advanced or metastatic Merkel cell carcinoma (MCC). ESMO. 2020: abstr. 1089P.
- Akkooi AV, Ascierto P, Nathan P, et al. A phase II, open-label study to investigate the efficacy and safety of domatinostat in combination with avelumab in patients with advanced unresectable/metastatic Merkel cell carcinoma progressing on anti-PD-(L)1 antibody therapy: The MERKLIN 2 study. J Clin Oncol. 2021; 39(15_suppl): TPS9592–TPS9592.
- Perrier A, Didelot A, Laurent-Puig P, et al. Epigenetic Mechanisms of Resistance to Immune Checkpoint Inhibitors. Biomolecules. 2020; 10(7).
- O’Day S, Perez C, Wise-Draper T, et al. 423 Safety and preliminary efficacy of intratumoral cavrotolimod (AST-008), a spherical nucleic acid TLR9 agonist, in combination with pembrolizumab in patients with advanced solid tumors. J Immunother Cancer. 2020; 8(Suppl 3): A449–A449.
- Study Evaluating Cemiplimab Alone and Combined With RP1 in Treating Advanced Squamous Skin Cancer (CERPASS). https://www.clinicaltrials.gov/ct2/show/NCT04050436?term=RP1&cond=Skin+Cancer&draw=2&rank=1.
- Study of RP1 Monotherapy and RP1 in Combination With Nivolumab (IGNYTE). https://www.clinicaltrials.gov/ct2/show/NCT03767348?term=RP1&cond=Skin+Cancer&draw=2&rank=2.
- A Study of SAR444245 Combined With Cemiplimab for the Treatment of Participants With Various Advanced Skin Cancers. https://www.clinicaltrials.gov/ct2/show/NCT04913220?term=cemiplimab&cond=Skin+Cancer&draw=2&rank=1.
- Lowe M, Yushak M, Delman K, et al. Winship 4851-19: A pilot study of neoadjuvant and adjuvant cemiplimab for high-risk cutaneous squamous cell carcinoma. J Clin Oncol. 2021; 39(15_suppl): TPS9593–TPS9593.
