ALTA-1L Trial in ALK+ mNSCLC
A review of the open-label, phase 3 ALTA-1L trial comparing the use of brigatinib to crizotinib in ALK+ metastatic non-small-cell lung cancer.
Joshua M. Bauml, MD: The ALTA-1L trial compared brigatinib at the dosing of 90 mg for the first 7 days followed by a dose escalation to 180 mg daily, if they tolerate it, compared to crizotinib. We found in that study that there was a remarkable improvement in progression-free survival with brigatinib, and there was a particularly great improvement in the incidence of brain metastases as a result of use with brigatinib. That’s not surprising given the fact that brigatinib has excellent CNS [central nervous system] penetrance, while crizotinib is relatively poor at that.
One of the concerns people have with the use of brigatinib is a pulmonary event; sometimes people erroneously call this pneumonitis, however it’s really not pneumonitis. There’s been wonderful work done on this by [Ross] Camidge, [MD, PhD,] at the University of Colorado. He found, along with his colleagues, in a paper published in the Journal of Thoracic Oncology, was that this is a pulmonary event. The distinction here is that pneumonitis implies there’s inflammation, and it further implies that if you stop the drug, it will get better. It turns out that both of those features do not apply to these pulmonary events. Giving steroids has no impact on the incidence of these events, and the best way to manage it, provided the patient is stable, is to continue treating through it. Then the patient can overcome it and continue to receive brigatinib safely the vast majority of the time. There’s been some recent work that Dr Camidge has led that has found these sorts of pulmonary events may be more common than what we see clinically if you look at pulmonary function test changes. But they seem to be brief and are not limiting in terms of causing severe toxicity for the vast majority of patients. If you look at the quality of life in the ALTA-1L study, you can see that brigatinib was associated with a better quality of life than crizotinib. However, it’s difficult to separate that from the simple fact that patients were responding longer to the treatment, and that is always associated with an improved quality of life.
This transcript was edited for clarity.
A 57-Year-Old Man with ALK+ NSCLC
Initial presentation
- A 57-year-old man presented with fatigue, anorexia, and occasional rib pain
- PMH: unremarkable
- PE: mild right-sided chest tenderness on palpation
Clinical workup
- Labs: WNL
- Chest x-ray showed multiple right upper lobe masses
- Chest/abdomen/pelvic CT scan confirmed 3 masses (largest 6.5 cm)
- PET scan showed activity in the right upper lobe masses
- MRI of the brain showed multiple scattered lesions, consistent with multifocal brain
- Bronchoscopy with transbronchial biopsy of the right upper lobe mass confirmed lung adenocarcinoma, invasive mediastinal
- Stage IV adenocarcinoma; ECOG PS 0
- Molecular testing: ALK fusion+, EGFR-, ROS1-, BRAF-, KRAS-, NTRK-, MET-, RET-, PD-L1 0% by IHC
Treatment
- Patient was started on brigatinib 90 mg qDay for 7 days; well tolerated; dose was increased to 180 mg qDay
