What is the next step in treatment for a patient with an actionable EGFR exon 19 mutation after completing carboplatin/pemetrexed chemotherapy?

From the Guidelines

For a patient with an actionable EGFR exon 19 mutation who has completed carboplatin/pemetrexed chemotherapy, the next step in treatment should be an EGFR tyrosine kinase inhibitor (TKI) such as osimertinib (preferred), or alternatives like gefitinib, erlotinib, or afatinib.

Key Considerations

• Osimertinib is typically administered at 80mg orally once daily until disease progression or unacceptable toxicity 1.
• This targeted therapy is more effective than continuing chemotherapy because EGFR exon 19 mutations are sensitizing mutations that make the cancer cells particularly responsive to EGFR TKIs.
• Patients should be monitored for common side effects including rash, diarrhea, and rarely, pneumonitis.
• Regular follow-up imaging (typically every 2-3 months initially) is recommended to assess treatment response.
• If the patient had previously progressed on an EGFR TKI before receiving chemotherapy, molecular testing should be performed to check for resistance mutations like T790M before determining the next treatment approach.

Treatment Options

• Osimertinib is the preferred treatment option due to its efficacy and safety profile 1.
• Alternatives like gefitinib, erlotinib, or afatinib may be considered based on patient-specific factors and preferences.
• Combination regimens, such as osimertinib with chemotherapy, may also be considered in certain cases 1.

Molecular Testing

• Molecular testing should be performed to confirm the presence of the EGFR exon 19 mutation and to check for resistance mutations like T790M 1.
• Next-generation sequencing (NGS) testing may be used to detect other potentially targetable mutations.

From the FDA Drug Label

Table 2 provides the recommended dosage of TAGRISSO by indication. ... First-line Treatment of EGFR Mutation-Positive Metastatic NSCLC 80 mg tablet orally once daily with or without food Until disease progression or unacceptable toxicity

The next step in treatment for a patient with an actionable EGFR exon 19 mutation after completing carboplatin/pemetrexed chemotherapy is to initiate osimertinib 80 mg orally once daily. This is based on the presence of the EGFR exon 19 mutation identified on NGS, which is an actionable mutation for osimertinib treatment 2.

From the Research

Next Steps in Treatment

The patient has completed carboplatin/pemetrexed chemotherapy and is in remission with no signs of progressive disease. Given the presence of an actionable EGFR exon 19 mutation, the next step in treatment is to initiate osimertinib 80 mg po daily, as planned, while waiting for approval.

Rationale for Osimertinib

• Osimertinib is a standard of care for EGFR-mutated non-small cell lung cancer (NSCLC) patients, as shown in studies such as 3 and 4.
• The efficacy of osimertinib in patients with mutations other than the common deletion in exon 19 and L858R in exon 21 is supported by studies like 3, which demonstrated activity in patients with uncommon EGFR-mutations.
• First-line treatment with osimertinib has been shown to lead to significantly longer progression-free survival than osimertinib monotherapy among patients with EGFR-mutated advanced NSCLC, as demonstrated in 4.

Considerations for Treatment

• The patient's performance status and ability to tolerate treatment should be considered, as highlighted in 5, which showed the efficacy and safety of first-line osimertinib treatment in patients with EGFR mutation-positive NSCLC and poor performance status.
• Molecular follow-up and detection of EGFR resistance mutations, such as C797S, are crucial in monitoring treatment response and potential resistance, as discussed in 6.
• Overall survival with osimertinib in untreated, EGFR-mutated advanced NSCLC has been demonstrated to be longer than with other EGFR-TKIs, as shown in 7.

Key Points

• Osimertinib is the planned next step in treatment for the patient with an actionable EGFR exon 19 mutation.
• The patient's treatment response and potential resistance should be closely monitored.
• Osimertinib has demonstrated efficacy and safety in patients with EGFR-mutated NSCLC, including those with poor performance status.