Amivantamab in the Treatment of Metastatic NSCLC: Patient Selection and Special Considerations

Petrini, Iacopo; Giaccone, Giuseppe

doi:10.2147/ott.s329095

Cited by 6 publications

(8 citation statements)

References 45 publications

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“…Considering the results, innovative treatments under development for the post-osimertinib and Pt-doublet setting, such as amivantamab, EGFR–mesenchymal epithelial transition factor bispecific antibody, and treatment combined with lazertinib (a third-generation EGFR-TKI) [ 31 ] and patritumab deruxtecan (human EGFR 3-directed monoclonal antibody–drug conjugate) [ 32 ], may be able to provide better treatment choices in this line of therapy.…”

Section: Discussionmentioning

confidence: 99%

Real-World Data About Treatment Outcomes for Patients with EGFR-Mutated NSCLC Resistance to Osimertinib and Platinum-Based Chemotherapy

Hayashi¹,

Nishio²,

Takahashi³

et al. 2023

Adv Ther

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Introduction Docetaxel is an established standard therapy after osimertinib and platinum-based doublet chemotherapy (Pt-doublet) for locally advanced or metastatic non-small cell lung cancer (NSCLC) with an epidermal growth factor receptor gene ( EGFR ) mutation. To facilitate future therapeutic developments in these patients after treatment with osimertinib and Pt-doublet, we estimated the outcomes of currently used post-treatment therapies. Methods Data of patients with NSCLC who received at least one medication after osimertinib and Pt-doublet between April 2008 and August 2021 were extracted from the Medical Data Vision claims database. The duration of treatment (DoT) (first treatment after osimertinib and Pt-doublet) and overall survival (OS) were estimated. The index date was the first day on which the medication was prescribed. Results In total, 731 patients (mean age 64 years) were screened. The most frequent post-treatments were docetaxel-based chemotherapy (30.2%), immune checkpoint inhibitor (ICI) alone or in combination (17.2%), first-/second-generation EGFR-tyrosine kinase inhibitors (16.7%), osimertinib (16.3%), and Pt-doublet (5.2%). The median DoT and OS (95% confidence interval) of all post-treatments were 3.5 (3.27, 3.77) and 10.3 (9.3, 12.1) months, respectively, reflecting the median DoT (3.8 months) and OS (10.0 months) of docetaxel-based chemotherapy. Among all post-treatment regimens, ICIs resulted numerically the shortest [2.77 (2.33, 3.00) months] and osimertinib the longest [4.40 (3.47, 5.67) months] median DoT. The median OS was shortest in patients post-treated with ICIs [7.07 (5.40, 9.90) months] and longest in patients rechallenged with Pt-doublet (12.27 months), followed by patients post-treated with osimertinib (11.70 months). In a subset analysis of patients who received first-line osimertinib and second-line Pt-doublet as well as Pt-doublet immediately after osimertinib, those post-treated with ICIs had the shortest median DoT. Conclusion Given the limited real-world efficacy on EGFR -mutant NSCLC resistant to osimertinib and platinum-based chemotherapy, the development of more highly potent post-treatment therapies is warranted.

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Section: Discussionmentioning

confidence: 99%

Real-World Data About Treatment Outcomes for Patients with EGFR-Mutated NSCLC Resistance to Osimertinib and Platinum-Based Chemotherapy

Hayashi¹,

Nishio²,

Takahashi³

et al. 2023

Adv Ther

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“…A recent ASCO (2022) study demonstrated that mobocertinib and amivantamab had similar efficacy in NSCLC patients with EGFR ex20ins who had disease progression during or after platinum-based chemotherapy. In the first-line study, PAPILLON (NCT04538664) ( 89 ), an international, multicenter, randomized, open-label, Phase III clinical trial, 308 patients were randomized (153 to amivantamab -chemotherapy and 155 to chemotherapy alone). The findings indicated that the amivantamab chemotherapy group achieved a significantly longer PFS than the chemotherapy group (median 11.4 vs. 6.7 months; hazard ratio for disease progression or death 0.40).…”

Section: New Therapeutic Strategies For Patients With Nsclc Who Have ...mentioning

confidence: 99%

Current status and breakthroughs in treating advanced non-small cell lung cancer with EGFR exon 20 insertion mutations

Hu,

Zhong,

Wang

et al. 2024

Front. Immunol.

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Recently, targeted therapy and immunotherapy have emerged as effective treatment options for non-small cell lung cancer (NSCLC). This progress has been facilitated by the rapid development of diagnostic and therapeutic technologies and the continuous research and development of new drugs, leading to a new era in precision medicine for NSCLC. This is a breakthrough for patients with common mutations in the human epidermal growth factor receptor (EGFR) gene in NSCLC. Consequently, the use of targeted drugs has significantly improved survival. Nevertheless, certain rare genetic mutations are referred to as EGFR exon 20 insertion (ex20ins) mutations, which differ in structure from conventional EGFR gene mutations, namely, exon 19 deletion mutations (19-Del) and exon 21 point mutations. Owing to their distinct structural characteristics, patients harboring these EGFR ex20ins mutations are unresponsive to traditional tyrosine kinase inhibitor (TKI) therapy. This particular group of patients did not fall within the scope of their applicability. However, the activating A763_Y764insFQEA mutation elicits a more pronounced response than mutations in the near and far regions of the C-helix immediately following it and should, therefore, be treated differently. Currently, there is a lack of effective treatments for EGFR ex20ins mutations NSCLC. The efficacy of chemotherapy has been relatively favorable, whereas the effectiveness of immunotherapy remains ambiguous owing to inadequate clinical data. In addition, the efficacy of the first- and second-generation targeted drugs remains limited. However, third-generation and novel targeted drugs have proven to be effective. Although novel EGFR-TKIs are expected to treat EGFR ex20ins mutations in patients with NSCLC, they face many challenges. The main focus of this review is on emerging therapies that target NSCLC with EGFR ex20ins and highlight major ongoing clinical trials while also providing an overview of the associated challenges and research advancements in this area.

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“…The CHRYSALIS trial demonstrated that amivantamab was effective in reducing tumor size and improving survival in patients with lung cancer with EGFR Ex20Ins mutation [ 7 ]. Table 1 shows the anti-EGFR antibodies approved for the treatment of lung cancer between 2004 and 2021, where it is demonstrated for different reasons that amivantamab is the best treatment option [ 8 ].…”

Section: Reviewmentioning

confidence: 99%

Amivantamab: A Novel Advance in the Treatment of Non-small Cell Lung Cancer

Zavaleta-Monestel,

García-Montero,

Arguedas-Chacón

et al. 2024

Cureus

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Amivantamab is a fully human bispecific monoclonal antibody indicated for treating patients with specifically large cell lung cancer. Its dosage is based on the patient's initial body weight and is administered via intravenous infusion after dilution. Therefore, this drug is given as a strategy due to the great need for a molecule targeting epidermal growth factor receptor (EGFR) and the mesenchymal-epithelial transition factor (MET), as acquired resistance to tyrosine kinase inhibitors (TKIs) was observed in the treatment of large cell lung cancer. This article encompasses a review of the benefits of amivantamab for patients with non-small cell lung cancer (NSCLC). This drug is the first therapy directed against this specific mutation, and unlike others, it could bind to two genetic receptors, whereas antibodies, in general, are directed toward a single receptor.

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Amivantamab in the Treatment of Metastatic NSCLC: Patient Selection and Special Considerations

Cited by 6 publications

References 45 publications

Real-World Data About Treatment Outcomes for Patients with EGFR-Mutated NSCLC Resistance to Osimertinib and Platinum-Based Chemotherapy

Real-World Data About Treatment Outcomes for Patients with EGFR-Mutated NSCLC Resistance to Osimertinib and Platinum-Based Chemotherapy

Current status and breakthroughs in treating advanced non-small cell lung cancer with EGFR exon 20 insertion mutations

Amivantamab: A Novel Advance in the Treatment of Non-small Cell Lung Cancer

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