Pfizer’s Lorbrena for Treatment of NSCLC Shows Positive Data in Phase 3 Trial

Pfizer has announced updated results from the phase 3 CROWN trial, which compared lorlatinib (Lorbrena) with crizotinib (Xalkori) for individuals with previously treated anaplastic lymphoma kinase (ALK)-positive advanced non–small cell lung cancer (NSCLC).

The analysis showed that, after a median follow-up of 3 years, lorlatinib continued to demonstrate meaningful improvement in progression-free survival assessed by blinded independent central review compared with crizotinib, corresponding to about a 73% reduction in the rate of death or progression.

The data was presented on April 12, 2022, at the American Association for Cancer Research Annual Meeting 2022.

“The long-term results from the CROWN trial confirm lorlatinib’s compelling safety and efficacy profile in the first-line setting, providing sustained benefit for up to 3 years for this patient population,” Chris Boshoff, MD, PhD, chief development officer of oncology at Pfizer Global Product Development, said in the statement. “Since its first-line approval based on the initial groundbreaking CROWN trial results, lorlatinib has solidified its place as a practice-changing medicine, and these updated data add to the growing body of evidence supporting its use from the onset of metastatic disease.”

In the analysis, investigators found that about 64% of individuals treated with lorlatinib were without disease progression after about 3 years compared with approximately 19% of individuals treated with crizotinib for the same amount of time.

As for the secondary endpoint, the objective response rate (ORR) was approximately 77% with lorlatinib and approximately 59% with crizotinib. Additionally, treatment with lorlatinib resulted in an approximate 92% reduction in the rate of intracranial progression.

The intracranial ORR for individuals with measurable brain metastases at baseline was approximately 83% with lorlatinib and approximately 23% with crizotinib, with an intracranial complete response rate of 72% and 8%, respectively.

For individuals without brain metastases at baseline, lorlatinib demonstrated a 98% reduction in the rate of intracranial progression.

“Approximately 25 to 40% of people with ALK-positive advanced non–small cell lung cancer either have brain metastases at diagnosis or develop brain metastases within 2 years after initial diagnosis, and biomarker-driven medicines like lorlatinib have transformed the way we treat this typically aggressive disease,” Benjamin Solomon, MBBS, PhD, a professor at the department of medical oncology at the Peter MacCallum Cancer Centre in Melbourne, Australia, said in the statement. “The new results from the CROWN trial confirm lorlatinib as a treatment option that significantly improves outcomes for people with previously untreated ALK-positive advanced NSCLC.”.

Investigators reported that the safety profile in the 3-year follow-up analysis was consistent with the established safety profiles with both drugs.

In the initial 2020 analysis, the most frequent adverse events (AEs) for those treated with lorlatinib were cognitive effects, diarrhea, dyspnea, edema, hypertriglyceridemia, peripheral neuropathy, and weight gain.

Serious AEs occurred in approximately 34% of individuals treated with lorlatinib, which included cognitive effects, dyspnea, pneumonia, pyrexia, and respiratory failure.

Investigators reported that fatal AEs occurred in approximately 3.4% of individuals treated with lorlatinib, and approximately 6.7% permanently discontinued the drug, because of AEs.

Reference

Three year follow-up data from phase 3 CROWN trial of Pfizer’s Lorbrena (lorlatinib) confirm prolonged progression-free survival in first-line ALK-positive advanced lung cancer. Pfizer. News release. April 8, 2022. Accessed April 12, 2022. https://www.pfizer.com/news/press-release/press-release-detail/three-year-follow-data-phase-3-crown-trial-pfizers