Imunoterapija prvič tudi za zdravljenje lokalno napredovalega nedrobnoceličnega pljučnega raka Immunotherapy for the first time in the treatment of locally advanced non-small cell lung cancer

Abstract

V zadnjih petnajstih letih smo priča hitremu razvoju na področju zdravljenja pljučnega raka, ki ostaja v svetovnem merilu še vedno rak z najvišjo obolevnostjo in umrljivostjo. Večina bolnikov z metastatsko boleznijo se zdravi s kemoterapijo (KT), tarčno zdravljenje je primerno za manj kot 20% bolnikov z nedrobnoceličnim pljučnim rakom (NDPR). V letu 2010 so nas navdušili rezultati raziskav na področju imunoterapije. Tumorske celice morajo biti prepoznane kot tuje telesu, da jih imunski sistem lahko odstrani. Vendar so tumorske celice razvile različne mehanizme za izmikanje imunskemu nadzoru, eden od teh je tudi sproščanje imunskih zaviralnih molekul kot je ligand programirane celične smrti (PD-L1), ki je glavni mediator imunosupresivnega delovanja. Zdravila, ki se trenutno uporabljajo za zdravljenje metastatskega NDPR, so monoklonska protitelesa proti PD-L1 ali PD-1. Z vezavo na PD-L1 ali njegov receptor PD-1 na imunskih celicah preprečijo imunosupresiven učinek in omogočijo uspešno delovanje aktiviranih T limfocitov. V Sloveniji sta registrirani dve zdravili z opisanim načinom delovanja, nivolumab in pembrolizumab. Na kongresu ESMO 2017 pa so bili predstavljeni rezultati raziskave PACIFIK, ki opisujejo dobrobit zdravljenja z imunoterapijo tudi pri lokalno napredovalih bolnikih z NDPR. Bolniki so po standardnem zdravljenju s kemoradioterapijo prejemali durvalumab ali placebo. V skupini, zdravljeni z durvalumabom, je bil čas brez napredovanja bolezni značilno daljši. Sinergistično delovanje obsevanja, ki je splošno priznan način lokalnega zdravljenja, v kombinaciji z imunoterapijo briše meje med sistemskim in lokalnim načinom zdravljenja raka, kar so pokazale tudi številne predklinične raziskave. Bodoče raziskave bodo podale odgovore, kateri način kombiniranja imunoterapije in obsevanja je najbolj primeren.

Abstract (Eng)

During the last fifteen years, we have witnessed rapid development in the field of the lung cancer treatment, which remains cancer with the highest morbidity and mortality worldwide. Most patients with metastatic disease are treated with chemotherapy, targeted treatment is appropriate for less than 20% of patients with non-small cell lung cancer (NSCLC). In 2010, we were impressed by the results of research from the field of immunotherapy. Tumor cells must be recognized as foreign in order to be removed by the immune system. However, tumor cells have developed various mechanisms to escape immune control, one of which is the release of immune inhibitory molecules such as the ligand programmed cell death (PD-L1), which is the principal mediator of immunosuppressive action. Medicinal products which are currently used to treat metastatic NSCLC are monoclonal antibodies against PD-L1 or PD-1. By binding to PD-L1 or its PD-1 receptor on immune cells, they prevent the immunosuppressive effect and enable the activated T lymphocytes to function successfully. In Slovenia, two medicinal products with the described mode of action are registered, nivolumab and pembrolizumab. At the ESMO 2017 Congress, the results of PACIFIC study showing benefit with immunotherapy treatment also in locally advanced patients with NSCLC were presented. Patients had received durvalumab or placebo after standard treatment with chemoradiotherapy. In the group treated with durvalumab, the progression-free survival was significantly longer. The synergistic effect of irradiation, a widely recognized method of local treatment, in combination with immunotherapy, blurs the boundaries between the systemic and local treatment of cancer, as has been shown by numerous pre-clinical studies. Future research will provide answers which method of combining immunotherapy and irradiation is most appropriate.