More highlights in Lung Cancer

Recent studies in EGFR-mutant advanced non-small cell lung cancer (NSCLC) include the MARIPOSA trial, showing that amivantamab/lazertinib results in significantly lower rates of MET and EGFR resistance alterations compared with osimertinib, and the MARIPOSA-2 trial, which demonstrated ongoing clinical benefits of amivantamab combined with chemotherapy, including improved overall survival (OS) and delayed progression, in patients who have progressed on osimertinib.

Lower rates of MET and EGFR resistance alterations with amivantamab plus lazertinib

The phase 3 MARIPOSA trial (NCT04487080) has recently shown significantly improved progression-free survival (PFS) with first-line amivantamab/lazertinib versus osimertinib in patients with EGFR-mutant advanced NSCLC [1]. Prof. Benjamin Besse (Institut Gustave Roussy, France) now presented results of required resistance mechanisms for participants of MARIPOSA with disease progression on amivantamab/lazertinib versus osimertinib [2]. Findings were based on ctDNA analyses in paired samples (baseline and end of treatment) of 140 participants in the osimertinib arm and 113 participants in the amivantamab/lazertinib arm.

Both acquired MET amplification and secondary EGFR resistance mutations were significantly lower in the amivantamab/lazertinib versus the osimertinib arm (MET amplification: 4.4% vs 13.6%; P=0.017; secondary EGFR resistance mutations: 0.9% vs 7.9%; P=0.014). Also, a lower rate of TP53/RB1 loss was observed in the amivantamab/lazertinib arm (0.9% vs 2.9%) as well a lower rate of alterations in ≥2 resistance pathways (27.8% vs 42.6%). In the amivantamab/lazertinib arm the presence of EGFR driver mutations decreased from 78.8% to 53.1%, whereas in the osimertinib arm this decreased from 82.9% to 72.1%.

Based on these results, Prof. Besse concluded that “amivantamab/lazertinib narrowed the spectrum and reduced the complexity of acquired resistance versus osimertinib.”

There are many options in the first-line setting for EGFR-mutant metastatic NSCLC, including the MARIPOSA regimen, a combination of osimertinib and platinum-based chemotherapy, and osimertinib. The understanding of optimal and individualised treatment sequences will be key in the future.

Ongoing clinical benefit of amivantamab plus chemotherapy in EGFR-mutant advanced NSCLC

Recently, the primary results of the phase 3 MARIPOSA-2 study (NCT04988295) demonstrated a significant progression-free survival (PFS) benefit of amivantamab/chemotherapy over chemotherapy alone in patients with in EGFR-mutant advanced NSCLC after disease progression on osimertinib (HR 0.48; 95% CI 0.36–0.64; P<0.01) [3]. Prof. Sanjay Popat (Royal Marsden Hospital, UK) now presented OS results at a median follow-up of 18.1 months [4].

The median OS was 17.7 months in the amivantamab/chemotherapy arm versus 15.3 months in the chemotherapy alone arm (HR 0.73; 95% CI 0.54–0.99; P=0.039). OS rate at 18 months was 50% and 40%, respectively. In addition, amivantamab favoured time to symptomatic progression (HR 0.73; 95% CI 0.55–0.96; P=0.026), time to discontinuation (HR 0.42; 95% CI 0.33–0.53; P<0.0001), time to subsequent therapy (HR 0.51; 95% CI 0.39–0.65; P<0.0001), and PFS after first subsequent therapy (HR 0.64; 95% CI 0.48–0.85; P=0.002).

“Longer MARIPOSA-2 follow-up results confirm the superior outcomes of amivantinib/chemotherapy over chemotherapy alone in EGFR-mutant advanced NSCLC patients after disease progression on osimertinib,” Prof. Popat concluded.

1. Cho BC, et al. N Engl J Med 2024;Jun 26. DOI: 10.1056/NEJMoa2403614.
2. Besse B, et al. Mechanisms of acquired resistance to first-line amivantamab plus lazertinib versus osimertinib in patients with EGFR-mutant advanced non-small cell lung cancer: An early analysis from the phase III MARIPOSA study. Abstract LBA55, ESMO Congress 2024, 13–17 September, Barcelona, Spain.
3. Passaro A, et al. Ann Oncol. 2024;35:77-90.
4. Popat S, et al. Amivantamab plus chemotherapy vs chemotherapy in EGFR-mutated, advanced non-small cell lung cancer after disease progression on osimertinib: Second interim overall survival from MARIPOSA-2. Abstract LBA54, ESMO Congress 2024, 13–17 September, Barcelona, Spain.

 

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Posted on 4 November 20244 November 2024