Second-Line Treatments in ALK-Rearranged NSCLC

Mohammad Jahanzeb, MD:In terms of his duration of stability after the initial response to alectinib, it’s a bit short. We expect it to be, on average, if you go by the data of the ALEX trial, which was the global study. There’s the J-ALEX trial also, which is similar for the Japanese population at half the dose. But the updated progression-free survival on the ALEX trial was 34 months. This patient progressed in only 9 months. His next line of therapy was brigatinib.

When this patient progressed, of course we had to choose a second-line therapy, and he received brigatinib, which is FDA approved for second-line use. It is not in the NCCN [National Comprehensive Cancer Network] guidelines, even for the first line. But this patient was started at the usual 90-mg-a-day dosage, which is to be done for a week before we raise it to 280 mg daily. This is the standard dosage that goes on until the patient progresses or can’t tolerate the drug. So that was done. This patient did not develop any pulmonary toxicity and actually tolerated this drug fairly well.

I would say brigatinib is a good choice because this patient had brain metastases and was on alectinib, which does penetrate into the brain. If you choose the next line of therapy, you want to choose something that does penetrate into the CNS [central nervous system], and brigatinib is an excellent choice for that.

Transcript edited for clarity.

Case: A 61-Year-Old Man WithALK-Rearranged NSCLC

• A 61-year-old man presented with recent onset shortness of breath and swelling above left clavicle.
• Relevant PMH:
  • Nonsmoker, no previous CV- or pulmonary-related complications
• PE: Lungs, right-sided wheezing on auscultation; left supraclavicular lymphadenopathy, palpable
• Diagnostic workup:
  • Labs: WNL
  • Lymph node biopsy showed adenocarcinoma
  • CT CAP showed a 2.5-cm solid pulmonary lesion in the left inferior lobe and multiple liver lesions
  • CT‐guided core needle biopsy of the lung lesion revealed lung adenocarcinoma
  • Molecular testing:
    • EGFR, BRAF, KRAS, MET, RET, NTRKwild-type
    • IHC;ALK-rearrangement
    • PD-L1 TPS, 0%
  • Contrast‐enhanced MRI of the head showed multiple brain metastases
• Treatment:
  • Started on alectinib 600 mg BID; achieved a partial response including regression of CNS disease
  • Patient developed grade 3 myalgia; dose reduced to 450 mg BID, sustained at grade 2
• Imaging at 9 months showed disease progression in the lung mass and liver; stable CNS disease
  • Lung biopsy, mutation analysis;ALKG1202R
• He was started on brigatinib 90 mg once daily and tolerated the dose well; after 1 week, her dose was increased to 180 mg once daily (2 90-mg tablets)
  • Partial response with significant shrinkage in lung, liver, and CNS lesions