Typical Response, Progression, and Second-Line Therapy for NSCLC

Jonathan W. Riess, MD, MS:The factors I consider in choosing second-line therapy include, and somewhat differ between, whether the patient was previously on crizotinib or were they on alectinib. So, previously, before the approval of alectinib as first-line treatment with crizotinib, the pattern of metastatic disease would play a role to some extent. So, for example, if there was one place of metastatic disease that was progressing, we would call that oligoprogression.

Oftentimes, I would think about giving focused radiations to that area and continuing crizotinib. Now I’ve done that a lot less with alectinib and brigatinib being approved for second-line treatment. But that is an option to consider, particularly for oligoprogression. If a patient’s more symptomatic or there are other areas of progression, I do think about switching to alectinib or brigatinib, and that’s clearly an indication for changing treatment from crizotinib to a next-generation ALK TKI. And often those patients can re-respond and have excellent responses to alectinib and brigatinib, including in the CNS where these drugs get excellent penetration across the blood—brain barrier. They can often have intracranial responses. So, another thing that I’ve done to help manage these patients is if the patients have asymptomatic brain metastases, I often do not use whole brain radiotherapy and often move to these ALK inhibitors. They have excellent blood–brain barrier penetration and excellent intracranial responses.

Transcript edited for clarity.

CASE:ALK+ Non—Small Cell Lung Cancer

March 2017

• A 69-year-old female never-smoker presented with dyspnea, cough and fatigue
• PMH: hypertension managed on losartan 100 mg
• Chest X-ray showed multiple bilateral lung nodules
• Brain MRI, negative for intracranial metastases
• Bronchoscopy was performed with a fine needle aspirate biopsy
  • Pathology revealed adenocarcinoma, consistent with a lung primary tumor
  • Molecular testing:
    • NGS: positive for ALK gene rearrangement
    • NGS: negative forEGFR, ROS1, RET, BRAF, KRAS
    • IHC: PD-L1 expression in 0% of cells
• The patient was started on therapy with crizotinib
• Follow-up imaging at 3 and 6 months showed marked regression of the lung mass, nodal spread, and bone lesions

January 2018

• After 10 months on crizotinib, the patient reported worsening fatigue, back pain, and dyspnea
• CT showed increased size of the pulmonary masses and bone lesions
• Brain MRI showed disseminated small lesions
• Crizotinib was discontinued and the patient was started on brigatinib