Amivantamab plus chemo improves survival in advanced NSCLC

Amivantamab plus chemotherapy with or without lazertinib results in longer progression-free survival (PFS), as well as intracranial PFS, compared with chemotherapy alone in patients with epidermal growth factor receptor (EGFR)-mutated advanced nonsmall-cell lung cancer (NSCLC) who had disease progression on or after osimertinib, results of the phase III MARIPOSA-2 study have shown.

“Amivantamab–chemotherapy and amivantamab–lazertinib–chemotherapy improved PFS and intracranial PFS versus chemotherapy in a population with limited options after disease progression on osimertinib,” the investigators said. “Longer follow-up is needed for the modified amivantamab–lazertinib–chemotherapy regimen.”

In MARIPOSA-2, 657 patients with EGFR-mutated (exon 19 deletions or L858R) locally advanced or metastatic NSCLC after disease progression on osimertinib were randomly assigned 2:2:1 to receive amivantamab–lazertinib–chemotherapy, chemotherapy only, or amivantamab plus chemotherapy.

PFS of amivantamab–chemotherapy and amivantamab–lazertinib–chemotherapy versus chemotherapy served as the primary endpoint.

“During the study, haematologic toxicities observed in the amivantamab–lazertinib–chemotherapy arm necessitated a regimen change to start lazertinib after carboplatin completion,” the investigators said.

The three treatment arms had well-balanced baseline characteristics, including by history of brain metastases and prior brain radiation. [Ann Oncol 2024;35:77-90]

Amivantamab plus chemotherapy (hazard ratio [HR] for disease progression or death, 0.48; p<0.001) and amivantamab–lazertinib–chemotherapy (HR, 0.44; p<0.001) significantly prolonged PFS relative to chemotherapy alone (median, 6.3 and 8.3 vs 4.2 months, respectively).

PFS improvements persisted in investigator assessment (HR for disease progression or death, 0.41 for amivantamab–chemotherapy and 0.38 for amivantamab–lazertinib–chemotherapy; p<0.001 for both; median, 8.2 and 8.3 vs 4.2 months, respectively).

The amivantamab–chemotherapy and amivantamab–lazertinib–chemotherapy arms also showed significantly higher objective response rate than did chemotherapy alone (64 percent and 63 percent vs 36 percent, respectively; p<0.001 for both).

Likewise, intracranial PFS was significantly longer with amivantamab–chemotherapy (HR for intracranial disease progression or death, 0.55) and amivantamab–lazertinib–chemotherapy (HR, 0.58) than with chemotherapy alone (median, 12.5 and 12.8 vs 8.3 months, respectively).

“The MARIPOSA-2 study shows that amivantamab–chemotherapy by itself can prevent or delay central nervous system recurrence,” the investigators said.

“A similar improvement was seen among patients with a history of brain metastasis who had not received prior brain radiation, strengthening this conclusion. The mechanism by which amivantamab improves intracranial PFS could either be through direct antitumour effects or indirectly through immune-based mechanisms,” they added.

In patients receiving amivantamab-containing regimens, common adverse events (AEs) included haematologic, EGFR-, and MET-related toxicities. Notably, haematologic AEs occurred less frequently with amivantamab‒chemotherapy than with amivantamab–lazertinib–chemotherapy.

“Amivantamab–chemotherapy has a manageable toxicity profile, as noted by the low rates of discontinuations of all study agents due to treatment-related AEs,” the investigators said. “It should be noted that it is likely that the safety profile of amivantamab–lazertinib–chemotherapy will improve by not giving all four drugs simultaneously.”