Next Steps in Treating ALK+ mNSCLC

Stephen Liu, MD: We have many agents that are active against ALK-positive non–small cell lung cancer. While we rely on response rate, progression-free survival, and overall survival as important outcomes in trials, it’s also important to look at patient quality of life and patient-reported outcomes [PROs]. This has been examined with brigatinib in the ALTA trial. As a reminder, the ALTA trial was a phase 2 trial looking at the safety and efficacy of brigatinib in ALK-positive lung cancer. The study did collect PRO data, and what it showed was there was an improvement in global health scores and quality-of-life scores. These improvements really suggest that patients live not only longer but better with the use of brigatinib. That’s consistent with clinical benefit, in my opinion.

In my practice, patients have done quite well with the use of brigatinib. Certainly, when cancer is under control, when we have high response rates, symptoms related to cancer decrease, which leads to an improvement in quality of life. I have found that adherence is very high with the use of brigatinib. For my patients who have cycled through multiple kinase inhibitors—crizotinib followed by brigatinib, alectinib followed by brigatinib—most have reported that the safety profile of brigatinib measures very favorably compared with other ALK kinase inhibitors.

I really think ALK fusion-positive lung cancer is 1 of the best examples of successful precision medicine. With identification of a fusion that can be seen on tissue or blood analysis, we can select highly effective treatments that last for years. To see progression-free survival measured in years, not months, is really quite remarkable and puts ALK fusion-positive disease far ahead of other fusion or molecular subtypes of lung cancer. This progress was made by rational drug design. It was made by intelligent and predicted drug biomarker development. However, there is certainly room for improvement. Understanding resistance will allow us to overcome and hopefully prevent resistance. Addition of chemotherapy may be an important strategy in the future because this has led to improvements in survival in EGFR-positive lung cancer.

One of the largest areas for improvement is immunotherapy. Immunotherapy is largely inactive in ALK-positive lung cancer. We need to understand why so we can overcome that and really deliver new modalities to patients with this subtype. However, the future is quite bright for ALK-positive lung cancer, with many active agents available and many more on the horizon.

Transcript edited for clarity.

Case: 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
• Imaging:
  • Chest x-ray showed 3 right upper lobe masses
  • Chest/abdomen/pelvic CT scan confirmed 3 masses (largest 7.3 cm)
  • PET scan showed activity in the right upper lobe masses
  • MRI of the brain showed widespread scatter small lesions; consistent with brain metastases
• Bronchoscopy with transbronchial biopsy of the right upper lobe confirmed lung adenocarcinoma
• Molecular testing: EML4-ALK fusion+, EGFR-, ROS1-, BRAF-, KRAS-, NTRK-, MET-, RET-, PD-L1 100%
• Staging: IVA adenocarcinoma; ECOG PS 0

Treatment

• Patient was started on brigatinib 90 mg qDay for 7 days; well tolerated; dose was increased to 180 mg qDay