Amivantamab/Chemotherapy Prolongs Progression-Free Survival in NSCLC

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Amivantamab-vmjw (Rybrevant) with chemotherapy significantly prolonged progression-free survival (PFS) at 13.9 months after first subsequent therapy vs 11.3 months (HR, 0.60; P = .017) with chemotherapy alone in patients with EGFR-mutant advanced non–small cell lung cancer (NSCLC). The study included patients who had experienced disease progression on osimertinib (Tagrisso). These findings were presented at the European Lung Cancer Congress 2024 in Prague, Czech Republic.¹

“At a median follow-up of 8.7 months, amivantamab with chemotherapy reduced the risk of progression or death by 52%,” Ryan D. Gentzler, MD, said in a presentation of the data. Gentzler is a thoracic medical oncologist and associate professor of medicine in the Division of Hematology/Oncology at the University of Virginia Cancer Center in Charlottesville.

The median PFS in the amivantamab/chemotherapy arm was 6.3 months (95% CI, 5.6-8.4) vs 4.2 months (95% CI, 4.0-4.4) in the chemotherapy-alone arm (HR, 0.48; 95% CI, 0.36-0.64); P = .001). The amivantamab/chemotherapy combination also significantly prolonged time to treatment discontinuation (TTD), time to start of subsequent treatment (TTST), and second PFS compared with chemotherapy alone.

In the phase 3 MARIPOSA-2 study (NCT04988295), a total of 657 patients with EGFR-mutated (exon 19 deletions or L858R) NSCLC were randomly assigned 2:2:1 to receive 1 of 3 combinations: amivantamab, lazertinib (Leclaza), and chemotherapy (n = 263); chemotherapy (n = 263); or amivantamab with chemotherapy (n = 131).² “[The] dosing schedule of the amivantamab, lazertinib, and chemotherapy arm was modified during the study. Results will be reported after additional follow-up,” according to study investigators.

At the median follow-up of 8.7 months, there were 42% of patients in the amivantamab/chemotherapy arm that progressed and 71% in the chemotherapy-alone arm. Among these, 35% of patients in the amivantamab/chemotherapy arm and 16% in the chemotherapy-alone arm continued treatment for an additional 4 weeks and reported a postprogression treatment duration of 18.3 weeks (95% CI, 9.0-not evaluable) vs 9 weeks (95% CI, 6.0-16.4), respectively.¹ Amivantamab with chemotherapy also significantly increased the time until disease progression when compared with chemotherapy alone, with a median of 11 vs 4.5 months (HR, 0.37; 95% CI, 0.28-0.50; P = .0001).

The median PFS after first subsequent therapy was 13.9 vs 11.3 months, respectively (HR, 0.60; 95% CI, 0.40-0.92; P= .017), and the TTST was 12.1 vs 6.6 months, respectively (HR, 0.42; P= .0001). Among patients with progressive disease (PD) and those treated beyond PD, 75% in the amivantamab/chemotherapy arm stopped treatment after disease progression vs 93% in the chemotherapy-alone arm. In both arms, 63% of patients with PD began subsequent systemic therapy. The most common subsequent treatments were osimertinib (10% in the amivantamab/chemotherapy arm and 9% in the chemotherapy arm) and docetaxel (7% vs 9%, respectively).

To be eligible for the trial, patients needed to have locally advanced or metastatic NSCLC, documented EGFR exon 19 deletion or L858R, have progressed on or after osimertinib monotherapy (as the most recent line), and an ECOG performance score of 0 or 1.¹

The study had 2 primary end points: PFS comparison between amivantamab with chemotherapy and amivantamab with lazertinib and chemotherapy vs chemotherapy alone. Secondary end points included objective response rate, duration of response, overall survival, intracranial PFS, safety, time to symptomatic progression, TTST, PFS after first subsequent therapy. The exploratory end point was TTD.

The onset and severity of hematologic adverse events (AEs) were monitored over time in the study. Laboratory tests were conducted weekly during cycle 1 for both treatment arms, with less frequent monitoring in subsequent cycles. It was observed that hematologic AEs, such as neutropenia, leukopenia, thrombocytopenia, and anemia, were most pronounced during cycle 1 with grade 1 to 4 AEs and tended to decrease as treatment progressed.

The severity of the AEs was found to be similar between both treatment arms from cycle 2 onward. However, in cycle 1, the amivantamab/chemotherapy arm produced AEs in approximately 45% of patients vs approximately 30% in the chemotherapy-alone arm. The primary AEs observed in the treatment regimens containing amivantamab were related to hematologic issues and toxicities associated with EGFR and MET inhibitors.² In the amivantamab/chemotherapy arm, there were lower rates of hematologic AEs compared with the amivantamab, lazertinib, and chemotherapy arm.

Amivantamab is an EGFR-MET bispecific antibody with immune cell–directing activity. Lazertinib is a highly selective, central nervous system–penetrant, third- generation EGFR tyrosine kinase inhibitor with efficacy in both activating EGFR mutations and T790M.¹ In phase 1 studies, the combination of amivantamab and carboplatin- pemetrexed chemotherapy, with or without lazertinib, showed effectiveness for the treatment of NSCLC with refractory EGFR mutations.

“[The] amivantamab/chemotherapy [combination] now stands as the new standard of care for patients with EGFR-mutant advanced NSCLC following disease progression on osimertinib,” according to study investigators.

REFERENCES:

1. Gentzler RD, Spira A, Melosky B, et al. Amivantamab plus chemotherapy vs chemotherapy in EGFR-mutant advanced NSCLC after progression on osimertinib: a post-progression analysis of MARIPOSA-2. Ann Oncol. 2024;9(suppl 3):1-53. doi:10.1016/esmoop/esmoop102569

2. Passaro A, Wang J, Wang Y, et al. Amivantamab plus chemotherapy with and without lazertinib in EGFR-mutant advanced NSCLC after disease progression on osimertinib: primary results from the phase III MARIPOSA-2 study. Ann Oncol. 2024;35(1):77-90. doi:10.1016/j.annonc.2023.10.117