Management of acquired resistance to EGFR TKI–targeted therapy in advanced non-small cell lung cancer (2024)

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Management of acquired resistance to EGFR TKI–targeted therapy in advanced non-small cell lung cancer (2024)

FAQs

How is EGFR mutation treated in non-small cell lung cancer? ›

EGFR inhibitors that target cells with an exon 20 mutation: Amivantamab (Rybrevant) in combination with chemo (carboplatin and pemetrexed). Amivantamab is a monoclonal antibody (a lab-made version of a specific immune system protein) that targets two proteins that help cancer cells grow: EGFR and MET.

What is resistance to TKI in NSCLC? ›

Mechanisms of primary resistance to EGFR-TKIs in NSCLC

The most important and frequent drug-resistant EGFR mutations are represented by an exon 20 insertion, whose frequency ranges from 1% to 10% of the total number of EGFR mutations.

What is the most common mechanism of EGFR TKI resistance? ›

The most common mechanism is the development of acquired EGFR T790M mutation [9]. T790M was found in about 50% of EGFR–mutant cases that acquired resistance to EGFR TKIs [9]. Patients using either first- or second-generation EGFR TKIs had a similar prevalence of acquired T790M [10].

What is the standard of care for EGFR mutated NSCLC? ›

Front-line epidermal growth factor receptor tyrosine kinase inhibitor (EGFR TKI) therapy is the standard of care for lung cancer patients with sensitising EGFR mutations (exon 19 deletion or L858R mutation).

What is the prognosis for NSCLC patients with EGFR? ›

In resected stage I to II NSCLC, EGFR mutations were found in 12.9% of cases, associated with a 5-year overall survival of 75%, with no impact on recurrence site, disease-free survival, and overall survival.

What is the first-line treatment for EGFR NSCLC? ›

For EGFR-mutant NSCLC patients with stable brain metastases, first-line options include osimertinib, gefitinib, erlotinib, afatinib, or a combination regimen (erlotinib + bevacizumab or gefitinib + pemetrexed + carboplatin).

What is the success rate of TKI? ›

The 10-year progression-free survival and overall survival (OS) rates were 81% and 87%, respectively. OS after 10-years, based on TKI exposure, was 100% (1 TKI), 82% (2 TKIs), 87% (3 TKIs), 75% (4 TKIs) and 55% (5 TKIs).

What is the first line of TKI treatment? ›

If you're diagnosed in the chronic phase, your first treatment will usually be a regular standard dose of one of three types of TKI: imatinib, dasatinib or nilotinib.

What TKIs are approved for NSCLC? ›

In RET-fusion positive NSCLC, the RET-selective TKIs selpercatinib and pralsetinib earned approval in 2021, as strong clinical activity was observed in the phase I/II LIBRETTO-001 and ARROW studies, both in treatment-naïve (ORR 84% and 72%, respectively) and previously treated patients (ORR 61% and 59%, respectively) [ ...

What are the side effects of EGFR-TKI drugs? ›

EGFR-TKI therapy is associated with side effects, primarily in the form of skin or gastrointestinal toxicities (e.g., skin rash or diarrhea). Although skin toxicities are not lethal or dose-limited, they frequently occur with EGFR-TKIs and affect patient quality of life (18).

What is the most commonly used TKI? ›

The three main TKI drugs currently used are:
  • Imatinib. Imatinib is the most commonly used TKI for CML. It can be used in any phase.
  • Nilotinib. Nilotinib can be used as a first treatment in the chronic phase. ...
  • Dasatinib. Dasatinib can be used as a first treatment in the chronic phase.

What is the response rate for EGFR-TKI? ›

In patients with active EGFR mutation, TKI therapy produces a high response rate up to 75%, which is comparable to the efficacy of palliative radiotherapy.

What is the gold standard for NSCLC treatment? ›

Stage II and IIIA adjuvant cisplatin-based chemotherapy remains the gold standard for completely resected NSCLC tumors.

What percentage of people have EGFR mutation in NSCLC? ›

A meta-analysis of 115,815 patients with NSCLC found the prevalence of EGFR mutations in stages I to III (29.9%–34.0%) to be comparable to that in stage IV (37.5%). 6.

What is the treatment after osimertinib resistance? ›

Resistance to osimertinib is attributed to a shift to a SCLC phenotype in 2–15% of cases [14,15,17,42]. Derived from primary SCLC, a platinum–etoposide combination therapy is routinely used to treat patients with SCLC transformation after osimertinib treatment.

What are the EGFR mutations in NSCLC patients? ›

Doctors group EGFR mutations in NSCLC into four types:
  • Classical EGFR mutations, which include the most common types: EGFR 19 deletions and EGFR L858R point mutations.
  • EGFR exon 20 insertions.
  • T790M-like mutations.
  • P-loop αC-helix compression (PACC) mutations.
Oct 11, 2023

How is EGFR exon 19 mutation treated? ›

Background. Clinical guidelines advise osimertinib as preferred first line treatment for advanced epidermal growth factor receptor (EGFR) mutated non-small cell lung cancer (NSCLC) with deletions in exon 19 (del19) or exon 21 L858R mutation.

What medication is used for EGFR positive lung cancer? ›

EGFR therapy refers to medications that bind to the EGFR protein and help to slow or stop cell growth. EGFR is present on the surface of some cells and can cause cells to divide when epidermal growth factor binds to it. Examples of EGFR therapy drugs include afatinib, dacomitinib, erlotinib, gefitinib, and osimertinib.

Is EGFR overexpression in non-small cell lung cancer? ›

These receptors play an important role for tumor cell survival and proliferation. EGFR overexpression has also been demonstrated in premalignant bronchial epithelium, suggesting that EGFR plays an important role in lung carcinogenesis. In lung carcinomas, EGFR is more commonly overexpressed than HER2/neu.

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