Lorlatinib for First-Line Treatment of ALK-Positive NSCLC
Posted: Thursday, December 3, 2020
According to Benjamin J. Solomon, MBBS, PhD, of the Peter MacCallum Cancer Centre, Melbourne, and colleagues, the third-generation ALK inhibitor lorlatinib appears to provide a significantly longer progression-free survival than crizotinib in patients with untreated ALK-positive non–small cell lung cancer (NSCLC). The interim data from the multicenter phase III CROWN trial were published in The New England Journal of Medicine.
“Biomarker-driven medicines have improved outcomes for people living with ALK-positive NSCLC, but innovative therapies are still needed to delay disease progression,” Dr. Solomon stated in a press release. “The results from the CROWN trial demonstrate that [lorlatinib] has the potential to be a practice-changing, first-line option.”
In a 1:1 ratio, untreated patients with locally advanced or metastatic ALK-positive NSCLC were randomly assigned to receive either oral lorlatinib (n = 149) or crizotinib (n = 147). Of the 296 enrolled patients, 291 received study treatment. Patients were stratified based on their ethnicity and brain metastasis status.
At 12 months, more patients treated with lorlatinib were alive and without disease progression than those treated with crizotinib (78% vs. 39%, respectively; P < .001). The objective response rates with lorlatinib and crizotinib were 76% and 58%, respectively. Among patients with measurable brain metastases, the intracranial response rate was 82% with lorlatinib and 23% with crizotinib. Most patients who received lorlatinib (71%) had an intracranial complete response.
Hyperlipidemia, edema, increased weight, peripheral neuropathy, and cognitive effects were among the most commonly reported adverse events with lorlatinib. More grade 3 and 4 adverse events were observed after treatment with lorlatinib than with crizotinib (72% vs. 56%, respectively); altered lipid levels occurred most frequently. A total of 7% and 9% of patients, respectively, discontinued treatment due to these toxicities.
Disclosure: For full disclosures of the study authors, visit nejm.org.