NCCN Adds 2 Category 1 Recommendations for Amivantamab in NSCLC Clinical Practice Guidelines

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The National Comprehensive Cancer Network (NCCN) has updated its Clinical Practice Guidelines for Non–Small Cell Lung Cancer (NSCLC) for 2024 to include 2 new category 1 recommendations for amivantamab-vmjw (Rybrevant) alongside chemotherapy in patients with treatment-naive, EGFR-mutated advanced NSCLC.¹

The first guideline update recommends the use of amivantamab plus carboplatin and pemetrexed as a preferred first-line therapy in treatment-naive patients with newly diagnosed advanced or metastatic EGFR exon 20 insertion–mutated, nonsquamous NSCLC.

The second update recommends the subsequent use of amivantamab plus chemotherapy with or without lazertinib for patients with NSCLC with EGFR exon 19 deletions or exon 21 L858R mutations who experienced disease progression after treatment with osimertinib (Tagrisso). The guidelines note that clinicians should consider a biopsy at time of progression to rule out small cell lung cancer transformation, and conduct biopsy or plasma testing to evaluate mechanisms of resistance.

These NCCN updates were supported by data from the phase 3 PAPILLON (NCT04538664) and MARIPOSA-2 (NCT04988295) trials, respectively.

PAPILLION

In the international, open-label PAPILLON trial, 308 patients with advanced NSCLC with EGFR exon 20 insertions without prior exposure to systemic therapy were randomly assigned 1:1 to receive intravenous amivantamab plus chemotherapy (n = 153) or chemotherapy alone (n = 155).² The primary end point was progression-free survival (PFS) according to blinded independent central review. Notably, patients in the chemotherapy group experiencing disease progression were permitted to cross over and receive amivantamab monotherapy.

The median PFS was 11.4 months in the amivantamab/chemotherapy arm vs 6.7 months in the chemotherapy group (HR, 0.40; 95% CI, 0.30-0.53; P < .001). Moreover, the 18-month PFS rate was 31% in the amivantamab/chemotherapy arm vs 3% in the chemotherapy arm. The overall response rates at the time of data cutoff were 73% and 47% in these groups, respectively (rate ratio, 1.50; 95% CI, 1.32-1.68; P < .001). An interim overall survival analysis showed that the combination reduced the risk of death vs chemotherapy by 33%, producing an HR of 0.67 (95% CI, 0.42-1.09; P = .11).

Regarding safety, the most common regimen-related adverse effects (AEs) were reversible hematologic and EGFR-related toxic effects. A total of 7% of patients discontinued amivantamab due to AEs.

MARIPOSA-2

This global, randomized, phase 3 trial enrolled patients with advanced NSCLC harboring documented EGFR exon 19 deletions or L858R mutations who had not received prior systemic therapy.³ Patients were randomly assigned 2:2:1 to receive amivantamab plus lazertinib and chemotherapy (n = 263), chemotherapy alone (n = 263), or amivantamab plus chemotherapy (n = 131).

At a median follow-up of 8.7 months, patients treated with amivantamab plus lazertinib and chemotherapy experienced a median PFS of 8.3 months vs 4.2 months with chemotherapy alone and 6.3 months with amivantamab plus chemotherapy. The addition of amivantamab to chemotherapy and the addition of amivantamab plus lazertinib to chemotherapy translated to 56% (HR, 0.48; 95% CI, 0.36-0.64 P < .001) and 52% (HR, 0.44; 95% CI, 0.35-0.56; P < .001) reductions in the risk of progression or death, respectively, compared with chemotherapy alone.

The 6-month PFS rates in the amivantamab/lazertinib/chemotherapy, amivantamab/chemotherapy, and chemotherapy arms were 59%, 51%, and 30%, respectively. The 12-month rates were 37%, 22%, and 13%, respectively. There were 62% (HR, 0.38; P < .001) and 59% (HR, 0.41; P < .001) reductions in the risk of disease progression or death with the respective amivantamab-based regimens vs chemotherapy alone.

Both amivantamab-based regimens also improved intracranial PFS vs chemotherapy.

A total of 72% of patients in the amivantamab plus chemotherapy arm experienced grade 3 or higher AEs compared with 92% of those in the amivantamab/lazertinib/chemotherapy arm and 48% of those in the chemotherapy arm. The most common grade 3 or higher AEs, occurring in 10% or more of patients, were neutropenia, thrombocytopenia, anemia, and leukopenia.

Findings from MARIPOSA supported the submission to the FDA of both a supplemental biologics license application and a new drug application seeking the approval of amivantamab plus lazertinib as frontline therapy in this population.⁴

References

1. NCCN. Clinical Guidelines in Oncology. Non-small cell lung cancer, version 1.2024. Accessed December 21, 2023. https://www.nccn.org/professionals/physician_gls/pdf/nscl.pdf
2. Zhou C, Tang KJ, Cho BC, et al. Amivantamab plus chemotherapy in NSCLC with EGFR exon 20 insertions. N Engl J Med. 2023;389(22):2039-2051. doi: 10.1056/NEJMoa2306441
3. Passaro A, Cho BC, Banuml JM, et al. Amivantamab plus chemotherapy (with or without lazertinib) vs chemotherapy in EGFR-mutated advanced NSCLC after progression on osimertinib: MARIPOSA-2, a phase III, global, randomized, controlled trial. Ann Oncol. 2023;34(suppl 2):S1307. doi:10.1016/j.annonc.2023.10.063
4. Johnson & Johnson submits supplemental biologics license application and new drug application to U.S. FDA seeking approval of RYBREVANT (amivantamab-vmjw) plus lazertinib for the treatment of patients with EGFR-mutated non-small cell lung cancer (NSCLC). News release. Johnson & Johnson. December 21, 2023. Accessed December 21, 2023. https://www.prnewswire.com/news-releases/johnson--johnson-submits-supplemental-biologics-license-application-and-new-drug-application-to-us-fda-seeking-approval-of-rybrevant-amivantamab-vmjw-plus-lazertinib-for-the-treatment-of-patients-with-egfr-mutated-non-small--302020967.html