Immunotherapy and lung cancer – An Update from the ELCC 2017

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Immunotherapy and lung cancer – An Update from the ELCC 2017

Immunotherapy in lung cancer has been a topic of very high interest and promise for several years now. Since the first positive phase 3 data have been presented at ASCO 2015, immunotherapy has become indispensible for NSCLC patients who are negative for clinically relevant biomarkers like ALK rearrangement and activating EGFR (discussed in a previous posting). Checkpoint inhibitors targeting PD1 at first and later also PD-L1 are approved after platinum-based chemotherapy in many countries worldwide with differences in the label e.g. as far as the PD-L1 biomarker is concerned. A relevant percentage of patients experience significant clinical benefit for a long duration of time (years!). Other patients do not respond as long and unfortunately, a third group of patients does not have a significant benefit regarding PFS and/or RR and other efficacy endpoints over chemotherapy (comparator arm in pivotal studies is a taxane as monotherapy).

The safety profile is superior compared to chemotherapy in all presented pivotal studies in second and later line thus far. However, there are of course side effects that have been reported and some of them are new for oncologists and include inflammation of different organs so called immune-related adverse events or irAE. This may not be surprising since immunotherapy of course affects the entire immune system and not only the environment of the cancer cells. The management of this novel type of therapy has required a change of mindset and the formation of different medical teams including endocrinologists and other specialists. It is really impressive how fast the community adjusted and how quickly the necessary treatment algorithms are already implemented at numerous hospitals. Protocols of management, monitoring and prevention of side effects were shared at the ELCC in educational sessions and will most likely remain an important topic at clinical research congresses for several years along with data of long-term treatment.

More recently data from clinical trials about immunotherapy in first line have been presented as well, which in some countries led to approval of a checkpoint inhibitor in first line as monotherapy in selected patients with high presence of the biomarker PD-L1 and in combination with chemotherapy in unselected patients. At the ELCC, the use of immunotherapy for first line treatment in NSCLC patient was frequently and controversially discussed. Several questions are still open and additional data from randomized trials are awaited to hopefully answer some of them. One major question is how to use immunotherapy in different patient groups e.g. patients that benefit from immunotherapy as mono-therapy, patients that might benefit from immunotherapy as a backbone with an add-on in form of chemo, radiation, targeted therapy or additional immunotherapy (different type) and patients that would require standard chemotherapy as a first treatment.

Consequently, the next question is how to identify patients of the different groups. PD-L1 is currently the only biomarker available but the research community agrees that this is not an ideal biomarker. The absence of an ‘ideal’ biomarker would predict that a patient will not benefit. Some PD-L1-negative patients, however, did show positive response to immunotherapy in clinical trials. How about a second biomarker? Would a combination of two biomarkers help with the selection of patients? Data presented at the AACR annual meeting and reviewed at the ELCC proposed that tumor mutational burden could be a potential biomarker. How to design the assay and how to implement this assay into clinical practice?

Getting all these questions presented as a listening person in the audience on “next steps” slides at research congresses is good. It shows that there is lots happening and great interest and hopefully promising times for patients in the future.

By | 2017-12-30T19:45:35+00:00 May 12th, 2017|Immunotherapy, Lung Cancer|0 Comments

About the Author:

Sanne has a mixed science/business background with a PhD in Mol. Oncology and an MBA in healthcare. She worked 12 years as a scientist in cancer research labs before she moved on towards life science/healthcare consulting and medical affairs. Sanne is inspired to function as a bridge to overcome gaps within the healthcare community through communication, medical education and support of clinical research ideas.

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