Conclusions
* ALK translocation define a 3-5% subgroup of lung adenocarcinomas in
younger never-smokers and are prognostically favourable.
* Crizotinib remains the 1L therapy in this context.
* Arguments in favor of front-line use of 2G ALK TKIs:
- Increase PFS compared to crizotinib (pending results-distinct tox!)
- “Protective effect” on CNS disease and CNS progression
- More aggresive and heterogeous resistance prevention
- 1L 2G TKIs may not preclude the use of crizotinib at PD
* Treatment should be individualized according to specific genotypes at
progression (role for plasma genotyping to avoid multiple biopsies).
* Combination strategies are needed to overcome off-target mechanisms of
resistance (including combinations with immunotherapy).
