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Salvage Surgery After First-Line Alectinib for Locally-Advanced/Metastatic ALK-Rearranged NSCLC: Pathological
Filippo Lococo1, Alessandra Cancellieri2, Marco Chiappetta1
1Unit of Thoracic Surgery, Fondazione Policlinico Gemelli IRCCS, Rome, Italy.
Background:
The role of salvage surgery after tyrosine kinase inhibitors in advanced oncogene-addicted non-small cell lung cancer is largely unexplored.
Patients:
We aimed to describe the pathological features and surgical early-outcomes of Anaplastic Lymphome Kinase anaplastic lymphome kinase positive non-small cell lung cancer patients undergoing surgery after first-line alectinib treatment. We retrospectively collected and analyzed multicentric data of 10 patients treated with alectinib for advanced-stage anaplastic lymphome kinase positive lung adenocarcinoma who underwent anatomical surgical resection from January 2020 to Decemeber 2021. All patients were treatment naive and received alectinib (600 mg twice daily). Surgery was always proposed after multidisciplinary discussion. The primary endpoints were pathological response and surgical feasibility (technical intraoperative complications, postoperative outcomes).
Results:
Alectinib was received for a mean of 212 days before surgery (42-415 days) and was generally interrupted about one week before surgery (range: 0-32 days) with no patient experienced grade 4 toxicity. All patients received an R0 resection with surgery consisting of lobectomy in 8 cases with bilobectomy and (left) pneumonectomy in 1 case each. Intra-operative difficulties were described in 7 cases (70%), mostly due to perivascular fibrosis or thickening of mediastinal lymph nodal tissues. Major and minor complications occurred in 0 and 3 cases (30%), respectively. A pathological complete response and major pathological response (defined as 0% and < 10% viable tumor cells, respectively) were observed in 50% and 90% of cases, respectively. Despite short follow-up, only one tumor recurrence was observed (in the only patient who did not resume alectinib after surgery).
Interpretation:
Despite some technical intraoperative difficulties, salvage surgery was safe and feasible after Alectinib for advanced lung adenocarcinoma.
Insights
Salvage surgery is safe and feasible for advanced Anaplastic Lymphome Kinase-positive lung cancer patients after alectinib treatment. This approach shows promising pathological responses and low recurrence rates, even with intraoperative challenges.
Area of Science:
- Oncology
- Thoracic Surgery
- Pharmacology
Background:
- The role of salvage surgery following tyrosine kinase inhibitor (TKI) therapy in advanced oncogene-addicted non-small cell lung cancer (NSCLC) remains under-investigated.
- Anaplastic Lymphome Kinase (ALK) positive NSCLC represents a subset where targeted therapies like alectinib are highly effective.
- Understanding the feasibility and outcomes of surgical intervention post-TKI treatment is crucial for optimizing patient management.
Purpose of the Study:
- To evaluate the pathological features and early surgical outcomes of ALK-positive NSCLC patients undergoing salvage surgery after first-line alectinib treatment.
- To assess the safety and feasibility of anatomical surgical resection in this specific patient cohort.
- To determine pathological response rates and early recurrence patterns post-surgery.
Main Methods:
- Retrospective analysis of multicentric data from 10 treatment-naive patients with advanced ALK-positive lung adenocarcinoma.
- Patients received first-line alectinib (600 mg twice daily) followed by anatomical surgical resection.
- Primary endpoints included pathological response (complete and major) and surgical feasibility (intraoperative and postoperative outcomes).
Main Results:
- Alectinib treatment duration averaged 212 days prior to surgery, with a short interruption before the procedure.
- All patients achieved an R0 resection, with lobectomy being the most common procedure (80%).
- Despite intraoperative difficulties in 70% of cases (fibrosis, nodal thickening), major complications were absent, and minor complications occurred in 30%. Pathological complete response (50%) and major pathological response (90%) were high, with only one recurrence observed.
Conclusions:
- Salvage surgery is a safe and feasible option for advanced ALK-positive lung adenocarcinoma patients following alectinib treatment.
- High rates of pathological response and low recurrence suggest a potential benefit of this multimodal approach.
- Careful multidisciplinary discussion and surgical planning are essential to manage potential intraoperative challenges.
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