Dr Mok on the Long-Term Efficacy of First-Line Lorlatinib in Advanced ALK+ NSCLC

“I can tell my patients that if they are progression free by the second year, they will have approximately a 79% chance that they may remain progression free at the end of the seventh year, which is an important message for patients.”

Tony Mok, BMSc, MD, FRCPC, FHKCP, FHKAM, FRCP, associate dean of Translation and Entrepreneurship, chairman of the Department of Clinical Oncology, and the Li Shu Fan Professor of Clinical Oncology at The Chinese University of Hong Kong, discussed data from the 7-year update of the phase 3 CROWN study (NCT03052608) investigating lorlatinib (Lorbrena) vs crizotinib (Xalkori) in the first-line setting in patients with advanced ALK-positive non–small cell lung cancer.

Mok emphasized that these long-term outcomes have been highly anticipated within the lung oncology community. The trial used a 1:1 randomization protocol, comparing a 100-milligram once-daily dose of lorlatinib (n = 149) against a 250-milligram twice-daily dose of crizotinib (n = 147). The trial also stratified for factors like the presence of brain metastases, as well as patient ethnicity.

Mok detailed how the primary end point of progression-free survival (PFS) has evolved over the course of several years. Initial data released in 2020 established a significant HR favoring the lorlatinib arm, and at the 60-month mark, most of the patient population remained progression free. As the study progressed to the 7-year analysis, Mok noted that the median PFS had still not been reached (95% CI, 68.5 months-not reached), with 55% of patients maintaining their progression-free status.

Furthermore, Mok focused on the longitudinal dynamics of disease progression within the trial. He noted a decreasing rate of events over time. In total, 20% of patients experienced progression events during the first year, and 10% of patients experienced progression events during the second year. Strikingly, in all years following the second, the progression event rates fell into the single digits. Mok explained that by the end of the second year of treatment, the PFS rate was 70%.

Mok emphasized the value of these long-term statistics for establishing a prognostic framework. He explained that if a patient successfully reaches 2 years without disease progression, they have a 79% chance of remaining progression free through the seventh year. This predictable pattern of enduring efficacy provides a critical message for patients, Mok concluded.