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Published on: February 12, 2017
Successful long-term outcome of neoadjuvant sequential targeted therapy and chemotherapy for stage III non-small cell
Masaya Aoki1, Ryo Miyata1, Go Kamimura1
1Department of General Thoracic Surgery, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Background:
Perioperative treatment of locally advanced non-small cell lung cancer (NSCLC) is attracting attention. The effect of neoadjuvant tyrosine kinase inhibitor (TKI) therapy on postoperative long-term outcomes in patients with driver gene mutations remains unclear. The aim of this study was to clarify the long-term survival outcomes of patients with stage III NSCLC harboring driver gene mutations who received preoperative TKI therapy.
Methods:
Between January 2016 and December 2018, 10 patients with clinical stage III NSCLC with driver gene mutations were treated with TKIs [epidermal growth factor receptor (EGFR) mutation, n=9; anaplastic lymphoma kinase (ALK) fusion, n=1]. One patient refused surgery. The remaining nine patients received sequential chemotherapy followed by surgery. Postoperatively, six patients received adjuvant chemotherapy, and TKIs were readministered in four patients.
Results:
The main adverse events of TKIs were grade 3 liver damage and grade 3 skin rash, which required a change in the drug from gefitinib to afatinib and dose reduction, respectively. In all 10 patients, the radiological response to TKIs was greater than the partial response, and nine patients underwent radical surgery. Although viable cancer cells remained in all patients with EGFR mutations, a pathological complete response was obtained in the patient with ALK fusion. No mortality or major morbidity was observed perioperatively. Of the patients who underwent surgery, 3 were alive without recurrence, while 6 had distant metastasis, including 5 with brain metastasis. Seven of the nine patients who underwent surgery were still alive after a median follow-up period of 77.2 months.
Conclusions:
Successful long-term outcomes were achieved after sequential targeted therapy and chemotherapy, followed by surgery for stage III NSCLC. However, it is noteworthy that postoperative treatment may have also contributed to minimizing postoperative recurrence.
Insights
Neoadjuvant tyrosine kinase inhibitor (TKI) therapy combined with chemotherapy and surgery shows promising long-term survival for stage III non-small cell lung cancer (NSCLC) patients with driver mutations. Postoperative treatments may further reduce recurrence.
Area of Science:
- Oncology
- Thoracic Surgery
- Pharmacology
Background:
- Perioperative treatment strategies for locally advanced non-small cell lung cancer (NSCLC) are evolving.
- The impact of neoadjuvant tyrosine kinase inhibitor (TKI) therapy on long-term outcomes in NSCLC patients with driver gene mutations is not well-established.
- This study investigates long-term survival in stage III NSCLC patients with driver mutations receiving preoperative TKI therapy.
Purpose of the Study:
- To evaluate the long-term survival outcomes of patients with stage III NSCLC and driver gene mutations who underwent preoperative TKI therapy.
- To assess the efficacy and safety of neoadjuvant TKI therapy in this patient cohort.
- To explore the role of sequential treatment regimens in improving patient prognosis.
Main Methods:
- A cohort of 10 patients with stage III NSCLC and driver gene mutations (EGFR or ALK) received neoadjuvant TKI therapy.
- Nine patients proceeded to sequential chemotherapy and surgery; one refused surgery.
- Postoperative management included adjuvant chemotherapy and TKI re-administration in select cases.
Main Results:
- Radiological response to TKIs was generally good, with nine patients undergoing radical surgery.
- Adverse events included grade 3 liver damage and skin rash, managed with dose adjustments or drug changes.
- After a median follow-up of 77.2 months, seven of nine surgically treated patients were alive, with three disease-free and six experiencing distant metastasis.
Conclusions:
- Sequential neoadjuvant targeted therapy, chemotherapy, and surgery can achieve successful long-term outcomes in stage III NSCLC with driver mutations.
- Postoperative treatment strategies appear crucial in minimizing recurrence.
- Further research is warranted to optimize perioperative management for improved survival in this population.
