In the first line of treatment, Rybrevant (amivantamab) plus Lazcluze (lazertinib) demonstrated improved clinical outcomes versus Tagrisso (osimertinib) in patients with advanced EGFR-mutant non-small cell lung cancer (NSCLC), according to a longer follow-up of the MARIPOSA study presented at the 2024 IASLC World Conference on Lung Cancer.
Specifically, the median overall survival (the time from the start of treatment when a patient with cancer is still alive) was not estimable compared with 37.3 months for Tagrisso. Of note, when overall survival is not estimable, it means that there was not enough information for researchers to determine this specific variable. At 3 years, 61% of patients on the Rybrevant plus Lazcluze combination remained alive versus 53% of those in the Tagrisso group.
“There was a trend in overall survival that favored [Rybrevant] plus [Lazcluze]. Median survival was not reached, whereas it was 37.3 months in patients treated with osimertinib [tagrisso],” Dr. Shirish M. Gadgeel, division head for hematology/oncology at Henry Ford Health, said during an oral presentation of the longer follow-up.
In the primary analysis, which was at a median follow-up of 22 months, Rybrevant plus Lazcluze showed a significant improvement in progression-free survival (length of time during and after treatment when a patient with cancer lives with the disease without worsening) compared with Tagrisso. An early interim overall survival analysis demonstrated a favorable trend for Rybrevant plus Lazcluze versus Tagrisso.
In August 2024, the FDA approved Rybrevant combined with Lazcluze for the first-line treatment of adult patients with locally advanced or metastatic NSCLC with EGFR exon 19 deletions or exon 21 L858R substitution mutations. The approval was based on the primary MARISPOSA data.
In MARIPOSA, 1,074 patients that did not receive treatment, EGFR-positive, locally advanced or metastatic NSCLC were randomly assigned to Rybrevant plus Lazcluze (429 patients), Tagrisso (429 patients), or Lazcluze (216 patients) to assess the contribution of components.
The primary measures assessed in the study were progression-free survival. The study also included secondary measures such as overall survival, intracranial progression-free survival (icPFS) (time without disease spreading to the brain), intracranial duration of response (icDoR; how long a treatment effectively controls disease within the brain), intracranial overall response rate (icORR; how many patients with brain metastases had a reduction or disappearance of their tumors after treatment), time to treatment discontinuation (TTD), time to subsequent therapy (TTST) and progression-free survival after first subsequent therapy.
At a median follow-up of 31.1 months, 185 of 421 patients and 145 of 428 patients remained on treatment of Rybrevant plus Lazcluze and Tagrisso, respectively. A total 155 patients and 233 patients from the respective arms were determined to have investigator-assessed progressive disease, therefore discontinuing treatment.
At 3 years, a favorable trend in icPFS survival was shown in the Rybrevant/Lazcluze arm, with sustained and durable central nervous system control. With a median follow-up of 31.1 months, the median icPFS was 24.9 months and 22.2 months in the Rybrevant/Lazcluze arm and Tagrisso arm, respectively. The 3-year landmark for icPFS was double for Rybrevant/Lazcluze (38%) compared with Tagrisso (18%).
At the 31.1-month median follow-up of 31.1 months, the median icDoR was not estimable and 24.4 months in the Rybrevant/Lazcluze arm and Tagrisso arms, respectively. The icORR was 77% in both arms; however, Rybrevant/Lazcluze demonstrated greater durability of response with improved icDoR versus Tagrisso.
The median TTD was 26.3 months and 22.6 months from the Rybrevant/Lazcluze and Tagrisso arms, respectively. At 3 years, more patients from the Rybrevant/Lazcluze arm remained on treatment (40%) than in the Tagrisso arm (29%).
Regarding TTST, the number of patients who experienced disease progression, discontinued treatment and started subsequent therapy was similar between the 2 arms, at 72% with Rybrevant/Lazcluze and 74% with Tagrisso. The median TTST was 30 months with Rybrevant/Lazcluze and 24 months with Tagrisso. In both arms, the most common subsequent therapy after discontinuing study treatment was paraplatin/alimta (carboplatin/pemetrexed) at 26% and 28%, respectively.
Additional findings showed that Rybrevant/Lazcluze significantly reduced the risk of second progression or death (PFS2) by 27%. The median PFS2 was not evaluable and 32.4 months in the Rybrevant/Lazcluze and Tagrisso arms, respectively. The 3-year landmark PFS2 rates were 57% and 49%, respectively.
“The MARIPOSA study is ongoing, and a prespecified final overall survival analysis with formal statistical testing will occur in the future. The FDA recently approved [the Rybrevant/Lazcluze] combination for the treatment of EGFR-mutant advanced non–small cell lung cancer for patients,” Gadgeel concluded.
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