During a Case-Based Roundtable® event, Christine Bestvina, MD, discussed the intracranial responses to repotrectinib for patients with ROS1-psotive non-small cell lung cancer in the first article of a 2-part series.
CASE SUMMARY
First-Line Therapy
Follow-Up Plan:
Targeted Oncology: How many patients in the phase 1/2 TRIDENT-1 trial (NCT03093116) had a central nervous system (CNS) metastasis?
CHRISTINE BESTVINA, MD: Thirty-six percent of patients at diagnosis [had a CNS metastasis], but at the time of diagnosis about half [of the patients] had CNS progression, if they’ve been on crizotinib.1 So, most patients will encounter brain metastases at some point in their disease trajectory. [In this study], 36 months is about as far out as we’re going for median intracranial progression, which is about the median [PFS] too.1
What were the response rates for patients with ROS1+ NSCLC who either had a CNS metastasis at baseline or later?
The objective response rate [ORR] in that population was about 90%. In patients without CNS metastasis, it’s also impressive [at 75% (95% CI, 62%-86%)] for those patients who were TKI naive....2 For the patients who had 2 prior TKIs, the response rates were not impressive [with an ORR of 40% (95% CI, 12%-74%) and no complete responses (CRs)]. Further, if they had brain metastasis but 2 prior ROS1 TKIs, then it was about a 12% response rate…and that arm of the trial was actually closed early.2 In general, I would say regardless of presence of brain metastases at diagnosis or not, it’s still very impressive responsive response rates [for TKI-naive patients and just 1 prior ROS1 TKI].
What safety concerns should be noted with this therapy?
The big safety point to [highlight] about this drug is dizziness.1 Dizziness of any grade occurs in about 60% of patients, and it can be grade 3 or higher in about 3% of patients. Outside of that, patients will...have paresthesia, [with 34% of any-grade paresthesia events occurring],1 and these can be very strange with [repotrectinib]. I had a patient who felt like his skin was on fire, and that was just how he continued to describe it. Dyspnea of a kind of unknown origin does occur with this drug, too. You’ll do a big workup, and it will all be negative, and it’s thought to just be dyspnea related to the drug.
You’ve got a few options [to help manage the dizziness]. There’s 2 weeks prior to dose escalation with this drug, a 2-week dose lead-in, and if the dizziness occurs in that time frame, you can decide [whether] you should increase the dose…. [If you do not increase the dose], then you would just leave the dose as is. If the dizziness does continue to be a problem later and the patient is on the full dose, then you have the option to dose reduce, and one-third of the patients in this trial were either dose reduced or dose interrupted due to toxicity.1
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