Numerous educational presentations, oral abstracts and satellite symposia (sponsored by industry) about ALK+ NSCLC were part of ELCC 2017.
The development for this type of lung cancer has been extremely rapid in the past 5-10 years. The number of patients is small – just about 5% of non squamous NSCLC patients have an ALK rearrangement (ALK+ NSCLC) that can be treated with an ALK inhibitor in first line (recommended by several guidelines e.g. NCCN, ESMO etc.) but also in later lines. In order to diagnose ALK+ NSCLC, patients need to be tested using immuno histochemistry (IHC) and/or FISH. The first ALK inhibitor was approved in 2011 (accelerated) first in 2nd line and later on also in 1st line (2014) in the US, Europe and other countries.
Unfortunately but not surprisingly, cancer cells develop resistance mechanisms so that in almost all patients, the primary and secondary tumors reappear or continue to grow after a first clinical benefit. This gave rise to the development of next generation (second, third, ….) of ALK inhibitors that showed great effects in patients whose tumor had become resistant to the first generation ALKi. Today’s understanding is that the most prominent mechanism of resistance would be the development of mutations in the ALK gene. A list of mutations has been established and it is now of high interest to detect the resistance mutation in an individual patient as fast as possible – potentially using a blood sample instead of tissue in a liquid biopsy approach. As a consequence, the next line of treatment would then include an ALKi that is able to overcome the resistance since not all ALK inhibitors are able to bind to certain ALK mutants. Diagnostic monitoring as well as therapeutic strategies are currently under debate. Different schools of thought exist among experts regarding the “what ALKi to use first” and the “how to sequence these inhibitors” that are available for prescription (4 ALKis) and will be available in the future (at least 2 or 3? Additional ALKis), “when to start testing?” patients for resistance mutations with “what assay?” and is “rechallenging an option?” with an inhibitor that was used previously? MedInContext believes this is a positive debate to have. The research community has not achieved a cure yet for these patients but might be much closer compared to 10 years ago. Clearly there are many more options available in the presence than in the past and potentially even more on the horizon including combinations with ALKi to be discussed some time in the future.