Immunotherapy for lung cancer effective even before surgery

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Blocking "switches" of the immune system has revolutionized the treatment of patients with various metastatic cancers. In 2018, the discovery of this principle was recognized by the Nobel Prize in Medicine. An international research team has now shown that the simultaneous inhibition of two "immune switches", PD-1 and LAG-3, can lead to the killing of lung cancer cells after just a few weeks. This promising therapeutic approach was recently reported on in the top journal "Nature Medicine".

Immunotherapy has now become an established part of the multimodal treatment of lung cancer, even in the early stages. To date, only PD-1 or PD-L1 inhibitors have been approved for this purpose. An international multicenter study led by Martin Schuler (Oncology) and Clemens Aigner (Thoracic Surgery), who has moved from Essen to the Medical University of Vienna, has now been able to show for the first time worldwide at centers in Germany, Belgium and the Netherlands that the LAG3 inhibitor Relatlimab in combination with Nivolumab can also be used safely for operable non-small cell lung cancer. All patients who were pretreated with either the combination or nivolumab alone in the study were able to undergo surgery with excellent perioperative results and an overall 1-year survival of 96 percent. In addition, mechanisms of response, resistance to therapy and genomic adaptation of the tumor were analyzed under the direction of Alexander Schramm (Tumor Research, University Medicine Essen).

As the study showed, the simultaneous blockade of two "switches" of the immune system directly before a lung cancer operation is possible. In some of the 60 participating patients, all tumor cells were killed before the operation by activating the body’s own immune response. Short-term immunotherapy prior to surgery therefore has great potential to increase the chances of curing lung cancer and at the same time reduce the burden of lengthy follow-up treatments for patients.

"Our study also helps to better understand the effect of immunotherapies in lung cancer," say the two principal investigators Martin Schuler from University Medicine Essen and Clemens Aigner from MedUni Vienna: "The aim of the research is to be able to offer individually tailored multimodal therapies to future patients with lung cancer."

Publikation: Nature Medicine

Neoadjuvant nivolumab with or without relatlimab in resectable non-20 small cell lung cancer: a randomized phase 2 trial.
Martin Schuler, Kristof Cuppens, Till Plönes, Marcel Wiesweg, Bert Du Pont, Balazs Hegedus, Johannes Köster, Fabian Mairinger, Kaid Darwiche, Annette Paschen, Brigitte Maes, Michel Vanbockrijck, David Lähnemann, Fang Zhao, Hubertus Hautzel, Dirk Theegarten, Koen Hartemink, Henning Reis, Paul Baas, Alexander Schramm and Clemens Aigner.
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