Safety of Surgery after Neoadjuvant Targeted Therapies in Non-Small Cell Lung Cancer: A Narrative Review

Abstract

New drugs, including immune checkpoint inhibitors and targeted therapy, have changed the prognosis in a subset of patients with advanced lung cancer, and are now actively investigated in a number of trials with neoadjuvant and adjuvant regimens. However, no phase III randomized studies were published yet. The current narrative review proves that targeted therapies are safe in neoadjuvant approach. Unsurprisingly, administration of therapy is related to an acceptable toxicity profile. Severe adverse events’ rate that rarely compromises outcomes of patients with advanced lung cancer is not that commonly accepted in early lung cancer as it may lead to missing the chance of curative surgery. Among those complications, the most important factors that may limit the use of targeted therapies are severe respiratory adverse events precluding the resection occurring after treatment with some anaplastic lymphoma kinase and rarely after epidermal growth factor receptor tyrosine kinase inhibitors. At this point, in the presented literature assessing the feasibility of neoadjuvant therapies with anaplastic lymphoma kinase and epidermal growth factor receptor tyrosine kinase inhibitors, we did not find any unexpected intraoperative events that would be of special interest to a thoracic surgeon. Moreover, the postoperative course was associated with typical rate of complications.

Neoadjuvant targeted therapy versus targeted combined with chemotherapy for resectable EGFR-mutant non–small cell lung cancer: a retrospective controlled real-world study

“…Judging from these data, the two schemes have little impact on the operation. A narrative review similar to our results suggests that neoadjuvant target therapy is well tolerated in resectable NSCLC patients, with all patients undergoing surgery without delay or major complications ( 27 , 28 ). Delays in surgery due to adverse events from oncology treatment, limitations in diagnostic services provided, and the possibility of progression during treatment may have challenged to the selection of neoadjuvant chemotherapy.…”

“…It is important to consider whether there is any toxicity that may delay or prevent the efficacy of surgery during neoadjuvant therapy. Compared to neoadjuvant chemotherapy, the use of EGFR inhibitors has fewer severe respiratory adverse events (including pneumonitis and interstitial lung disease), which could limit the use of neoadjuvant therapy ( 27 ).…”

Neoadjuvant Targeted Therapy in Resectable NSCLC: Current and Future Perspectives

“… 81 , 82 Rare cases of severe respiratory adverse events (AEs) (including pneumonitis and interstitial lung disease) have been reported with some ALK, EGFR, and MET inhibitors, which could limit the use of these therapies before surgical resection. 83 , 84 Other reported rare toxicities that may impact surgery include the following: cardiotoxicity (osimertinib), 85 , 86 bradycardia (alectinib and crizotinib), 87 , 88 thrombocytopenia (osimertinib), 89 fever (dabrafenib plus trametinib), 90 hepatotoxicity (sotorasib), 91 and CNS toxicity (lorlatinib). 92 Preliminary results from the ALK -positive cohort of the NAUTIKA1 study demonstrated that neoadjuvant alectinib was well tolerated in patients with resectable NSCLC, and to date, all patients have undergone surgery without delays or major complications.…”

MYH16 upregulation is associated with lung adenocarcinoma aggressiveness and immune infiltration

“…The development of novel therapeutic strategies has remarkably enhanced the survival outcomes of patients with LUAD. [ 7–11 ] Immune checkpoint inhibitors (ICIs) targeting programmed cell death 1/ligand 1 (PD‐1/PD‐L1) can induce an effective antitumor role in these patients. [ 12,13 ] However, not all patients respond to ICIs, and their overall survival (OS) outcomes necessitate further improvement.…”