ALTA-1L Trial: Brigatinib
Karen Reckamp, MD, discusses the design, practical implications, and important findings from the ALTA-1L clinical trial.
Karen Reckamp, MD: In thinking of the design of the ALTA-1L trial, which was published in 2019, brigatinib is a specific ALK inhibitor and overcomes many of the mechanisms of resistance associated with crizotinib and alectinib. Patients first receive a 7-day run-in of the 90-mg tablets followed by 180 mg, if well tolerated. This was shown to have an improvement in progression-free survival over the use of crizotinib. There was a significant benefit in a delay to brain metastasis and in control of brain metastasis. There was a prolonged duration of response, and much of this has not yet been reached as the initial follow-up is still shorter than what we’ve seen with alectinib.
We know from that frontline trial that these numbers continue to lengthen as the follow-up goes on. For adherence to this medication, brigatinib is a once-daily drug, and it comes in both 90-mg and 180-mg tablets, which makes it easy for a patient to take once a day. In these patients, they’re starting with 90 mg, and we’re evaluating for any pulmonary symptoms, and if they can tolerate it over the first week, they are increased to 180 mg. We’re checking in with patients by phone call and evaluating after that first week and then after the first week on 180 mg. These are generally phone calls, and the visits don’t change based on utilizing brigatinib. Patients tolerate these medications well, and the quality of life is significantly improved on brigatinib when they’re starting to experience tumor regression on the drug.
We were part of the second-line study utilizing brigatinib and have many patients who have had excellent responses, and some who are still on brigatinib years later with continued tumor response. In addition, we’re just starting to use brigatinib in the frontline setting, but several patients are doing well and tolerating the brigatinib without significant toxicity. Most patients are able to go up to the 180 mg, though I’ve had some who have required staying at the 90-mg dose.
Transcript edited for clarity.
Case: A 68-Year-Old Woman with ALK+ Non–Small Cell Lung Cancer
Initial presentation
- A 68-year-old woman presented with fatigue, wheezing and decreased appetite
- PMH: unremarkable
- PE: wheezing on auscultation; ECOS PS 1
Clinical Workup
- Labs: WNL
- Chest x-ray showed a left lower lobe mass
- Chest/abdomen/pelvic CT scan confirmed a 6.8-cm left lower lobe lung mass and a suspicious liver lesion
- PET scan showed activity in the left lower lobe mass and liver
- MRI of the brain showed several subcentimeter lesions without edema
- Bronchoscopy with transbronchial biopsy of the left lower lobe mass confirmed lung adenocarcinoma
- Molecular testing: NGS revealed EML4/ALK fusion+, EGFR-, ROS1-, BRAF-, KRAS-, NTRK-, MET-, RET-, PD-L1 0% by IHC
- Staging: IVB adenocarcinoma
Treatment
- Patient was started on brigatinib 90 mg qDay for 7 days; well tolerated; dose was increased to 180 mg qDay
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