Introduction - ALK rearrangement a distinct subset of non small cell lung cancer(NSCLC), incidence 2-7% highly sensitive, effectively treated with ALK TKI inhibitors. Different generations of ALK TKI increases the outcome of ALK positive lung cancer with sequencing the therapy with interim molecular testing for resistant mutation.
Methods - A 48 years male, never smoker presented in July 2017 with hemoptysis. PET CT - left hilar mass (2.4x1.3cm), bilateral lung nodules, lytic bone lesion with biopsy confirming adenocarcinoma. Diagnosed as adenocarcinoma lung with bone metastasis. Molecular testing (IHC) revealed EML4-ALK rearrangement. He was started on Alectinib 600mg twice daily with zoledronic acid from Aug 2017. He tolerated therapy with no side effects.
Results - Interim CT thorax (Dec 2017) showed partial response and Aug 2018 PET CT scan showed partial metabolic response. In Aug 2019, PET CT scan showed progressive hilar mass (3.2x2cm). He underwent re-biopsy confirming adenocarcinoma. NGS(Foundation One) report - EML4 -ALK G1202R mutation. Considering isolated progressive hilar mass he received SBRT and started on Lorlatinib 100mg daily (Sep 2019). Initial month he developed bilateral edema of legs, difficulty in walking and managed conservatively. Follow up PET CT scan (July 2021) showed complete metabolic response. He stopped therapy on his own from July 2021,he later developed significant loss of weight,hoarseness of voice with ECOG PS 3. In Dec 2021, PET CT scan showed progressive left hilar mass (2.2x1.6cm), increasing metabolic activity with bone lesions, he was restarted on Lorlatinib(Jan 2022) with X geva. PET CT scan (July 2022) - total resolution of hilar mass, bone lesions. Tolerated well with grade 2 hypertriglyceridemia, ECOG PS is 1. Hence our patient with a sequential approach have a durable ongoing OS of 5 years.
Conclusion - Presence of ALK gene predicts strong sensitivity to ALK inhibitors with excellent overall survival. Sequencing ALK inhibitor therapy has an impact on improving OS. Molecular testing and looking for ALK resistance mutation helps to choose Lorlatinib, the only sensitive TKI which targets (G1202R). This is an evolving precision based therapy, improves outcome in lung cancer.