Thoracic: Lung Cancer
Clinicopathologic outcomes of preoperative targeted therapy in patients with clinical stage I to III non–small cell lung cancer

Read at the 102nd Annual Meeting of The American Association for Thoracic Surgery, Boston, Massachusetts, May 14-17, 2022.
https://doi.org/10.1016/j.jtcvs.2022.10.056Get rights and content

Abstract

Objective

Targeted therapy improves outcomes in patients with advanced-stage non–small cell lung cancer (NSCLC) and in the adjuvant setting, but data on its use before surgery are limited. We sought to investigate the safety and feasibility of preoperative targeted therapy in patients with operable NSCLC.

Methods

We retrospectively reviewed 51 patients with clinical stage I to III NSCLC who received targeted therapy, alone or in combination with chemotherapy, before surgical resection with curative intent, treated from 2004 to 2021. The primary outcome was the safety and feasibility of preoperative targeted therapy; secondary outcomes included objective response rate, major pathologic response (defined as ≤10% viable tumor) rate, recurrence-free survival (RFS), and overall survival.

Results

Of the 51 patients included, 46 had an activating epidermal growth factor receptor gene alteration and 5 had an anaplastic lymphoma kinase fusion. Overall, 37 of 46 evaluable patients experienced at least 1 adverse event before surgery; however, only 3 patients experienced a grade 3 or 4 event. The objective response rate was 38% (17/45) for all evaluable patients and 44% (14/32) for patients with clinical stage II or III disease. The major pathologic response rate was 20% (9/44); 2 patients had a complete pathologic response. Median RFS was 3.8 years (95% CI, 2.8 to not reached). Targeted therapy alone was associated with better RFS than combination therapy (P = .009) in patients with clinical stage II or III disease.

Conclusions

Preoperative targeted therapy was well tolerated and associated with good outcomes, with or without induction chemotherapy. In addition, radiographic response and pathologic response were strongly correlated.

Section snippets

Patient Cohort

This study was approved by the institutional review board at Memorial Sloan Kettering Cancer Center, and all patients gave informed consent (MSK IRB 16-1395; approved August 26, 2016). We retrospectively reviewed data of patients with NSCLC who were treated from January 2004 to April 2021 with targeted therapy before surgical resection with curative intent. At the time of initial evaluation at our institution, all patients were planned to receive surgical resection after completion of their

Demographic Characteristics

In total, 51 patients met inclusion criteria, of whom 90% (46/51) had an EGFR alteration and 10% (5/51) had an ALK fusion. Of the overall cohort, 35 were women (35/51 [69%]), and 27 (27/51 [53%]) were never-smokers. The median age at surgery was 64 years (interquartile range, 55-72 years). Most patients (46/51 [90%]) underwent lobectomy, and all patients had an R0 resection. Surgical approach evolved over the course of the study, with most earlier patients having undergone open resection (27/51

Discussion

Targeted therapies are associated with longer survival among patients with advanced-stage NSCLC and when given as adjuvant therapy after complete surgical resection.8,12,16,18 In contrast, only a few studies, primarily in East Asian populations,35,36 have examined the use of TKIs in the neoadjuvant setting.20,21,37,38 Our study is, to our knowledge, the largest retrospective study, to date, to investigate preoperative TKI use in patients with activating EGFR mutations and ALK fusions. We found

Conclusions

Preoperative TKI targeted therapy was well tolerated in patients with clinical stage I to III NSCLC with actionable EGFR and ALK alterations (Figure 4). In addition, radiographic response strongly correlated with pathologic response, and preoperative targeted therapy, even when used alone, was associated with good RFS and OS.

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  • Cited by (2)

    This work was supported by National Institutes of Health grants R01CA217169 and R01CA240472 (both to D.R.J.), National Institutes of Health grant R01CA236615 (to P.S.A.), Hamilton Family Foundation (to D.R.J.), Al-Asmakh Foundation (to D.R.J.), US Department of Defense grant LC160212 (to P.S.A.), and National Institutes of Health grant P30CA008748 (to Memorial Sloan Kettering Cancer Center).

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