Frontline Treatments in ALK-Rearranged NSCLC

Mohammad Jahanzeb, MD:I’m Dr Mohammad Jahanzeb with Florida Precision Oncology, of 21st Century Oncology.

This was an interesting case of a 61-year-old white man who had never really smoked and presented with swelling above his left clavicle and shortness of breath. His examination was really remarkable for some wheezing in the chest. Otherwise, the case was fairly unremarkable. His laboratory data [were] also unremarkable. He had a biopsy of his left supraclavicular lymph node, which showed adenocarcinoma of the lung. Then he had an additional biopsy of the liver, because a CT [computed tomography] scan of his chest, abdomen, and pelvis showed evidence of liver metastases.

Interestingly, when molecular studies were sent, the patient had anALKrearrangement. None of the other mutations were found. His PD-L1 [programmed death-ligand 1] was 0%. To complete his staging work-up, he had an MRI [magnetic resonance imaging] of the brain, which showed multiple brain metastases.

When you think of this patient, what’s a little unusual is that his age is slightly above what we expect for anALK-positive patient. That’s a bit of an unusual feature. Otherwise, it’s very common to have brain metastases. It’s common to be metastatic at the onset, at the time of diagnosis. This is a fairly aggressive disease that has a predilection for brain metastases.

In this case, we chose to give him alectinib, which is FDA approved for first-line use besides some others that we can talk about later. The patient developed some toxicities on alectinib, specifically myalgias. The [dosage] had to be reduced from 600 mg down to 450 mg a day. The toxicity was maintained at about a grade 2 level. Ultimately, we had to follow him with imaging, and he progressed after 9 months.

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