A post-progression analysis of data from MARIPOSA-2 showed that following disease progression on osimertinib, patients with EGFR-mutated advanced non-small cell lung cancer (NSCLC) had significantly prolonged time to treatment discontinuation, time to subsequent therapy, and progression-free survival after subsequent therapy when treated with amivantamab plus chemotherapy compared to chemotherapy alone.
The results were presented by Ryan D. Gentzler, MD, Associate Professor of Medicine in the Department of Hematology/Oncology at the University of Virginia, Charlottesville, on March 21 during the European Lung Cancer Congress.
During his presentation, Dr. Gentzler focused on secondary and exploratory endpoints from the amivantamab plus chemotherapy and chemotherapy arms of the randomized, phase III MARIPOSA-2 trial, which also had a third arm that combined amivantamab, lazertinib, and chemotherapy. The results for the primary endpoint—progression-free survival—were previously presented and showed amivantamab-chemotherapy reduced the risk of progression or death by 52%. The median progression-free survival (PFS) with amivantamab-chemotherapy was 6.3 months versus 4.2 months for chemotherapy alone.
Looking at the secondary endpoints, Dr. Gentzler said the median time to treatment discontinuation was longer with amivantamab-chemotherapy compared to chemotherapy, with a median of 11.0 months and 4.5 months, respectively. The hazard ratio was 0.37 and the P value less than 0.0001.
“Additionally, in the amivantamab-chemotherapy arm, 42% of patients had progression of disease versus 71% in the chemotherapy arm,” he said. “Among those with disease progression, 35% of patients continued treatment beyond progression with the amivantamab-chemotherapy versus only 16% in the chemotherapy alone arm. The median duration of treatment post progression was 18.3 weeks with amivantamab-chemotherapy and 9 weeks with chemotherapy alone.”
Time to subsequent therapy was also significantly longer with the amivantamab-chemotherapy combination at 12.1 months versus 6.6 months with a hazard ratio of 0.42. In both arms, 63% of patients with disease progression and discontinuation of study treatment received a subsequent therapy, Dr. Gentzler said. Subsequent therapies were prescribed at investigator discretion. The most common were single agent chemotherapy or TKI alone, he said. The specific agents that were most prescribed were osimertinib and docetaxel.
“Looking at progression-free survival after second disease progression, this endpoint was also statistically significantly improved with the combination of amivantamab plus chemotherapy at 13.9 months versus 11.3 months,” Dr. Gentzler said. “The hazard ratio here of was 0.60 with a P value of 0.017. Due to the potential for interactions of hematologic adverse events and these post-progression analysis endpoints, we sought to further look at this in more detail over time. Hematologic adverse events were more common in cycle one in both arms of the study, numerically higher in the chemotherapy and amivantamab arm. It’s also worth noting that these laboratory assessments were conducted once a week due to the scheduling of dosing amivantamab during cycle one, but when you look at cycles two through four and five and beyond, these adverse events are fairly similar between the two arms.”
Dr. Gentzler concluded that compared to chemotherapy, amivantamab-chemotherapy in patients with EGFR-mutated advanced NSCLC after disease progression on osimertinib significantly prolonged the endpoints of time to treatment discontinuation, time to subsequent therapy, and progression-free survival after subsequent therapy.
“And while it appears as though there was higher incidence and severity of hematologic adverse events in the amivantamab-chemotherapy arm, this was really restricted to cycle one, and the profiles were similar in subsequent cycles,” he said. “So, in conclusion, amivantamab-chemotherapy represents a new standard of care among patients with EGFR-mutant advanced non-small cell lung cancer after disease progression on osimertinib.”
