[Operability and Pathological Response of Non-Small Cell Lung Cancer (NSCLC) after Neoadjuvant Therapy with Immune
E Lücke1, C Ganzert1, S Föllner1
1Klinik für Pneumologie, Otto-von-Guericke-Universität Magdeburg, Magdeburg.
Background:
The blockade of immune escape mechanisms (e. g. PD1 /PD-L1) using immune checkpoint inhibition (ICI) can significantly prolong survival and induce remission in patients with advanced non-small cell lung cancer (NSCLC). Less is known about neoadjuvant ICI in patients with resectable (UICC stage III) or oligometastatic (UICC stage IVa) NSCLC.
Methods:
Tissue biopsies from patients with advanced or oligometastatic NSCLC were screened for PD-L1 expression. In case of PD-L1-expression > 50 %, ECOG status of 0 or 1 and expected operability, patients received ICI. After about four weeks, patients underwent thoracic surgical resection. In all patients, a complete staging, including PET-CT, cMRI, and endobronchial ultrasound, was performed. The tolerability, the radiological and the histopathological tumor response as well as the surgical and oncological outcomes were analyzed.
Findings:
Four patients (2 male, 2 female, age 56 - 78 years, n = 3 adenocarcinoma, n = 1 squamous cell carcinoma) with local advanced tumors received ICI before surgical resection. In three cases the mediastinal lymph nodes were positive. One patient had a single cerebral metastasis which was treated with radiotherapy. All four patients underwent therapy with two to six cycles of ICI (3 × pembrolizumab, 1 × atezolizumab) without any complication, and ICI did not delay the time of surgical resection. According to iRECIST, three patients showed partial response (PR), one patient had stable disease (SD). All tumors were completely resected. The thoracic surgical procedures proved to be technically unproblematic despite inflammatory changes. There were neither treatment-related deaths nor perioperative complications. In the resectates, complete pathological response (CPR, regression grade III ) and regression grade IIb were detected twice. The average time of follow-up was 12 (1 - 24) months. Patients with PPR developed distant metastasis after six months or a local recurrence after four months. The CPR patient is relapse free to date.
Conclusion:
In selected patients, neoadjuvant therapy with ICI is well tolerated and can induce a complete remission of the tumor. Treatment with ICI has no negative impact on the surgical procedure. Prognosis seems to be promising in CPR and limited in PPR.
Insights
Neoadjuvant immune checkpoint inhibition (ICI) in advanced non-small cell lung cancer (NSCLC) is well-tolerated and does not impede surgery. This approach can lead to complete tumor remission in selected patients, offering promising outcomes for those with a complete pathological response.
Area of Science:
- Oncology
- Immunotherapy
- Thoracic Surgery
Background:
- Immune checkpoint inhibition (ICI) targeting PD1/PD-L1 pathways shows efficacy in advanced non-small cell lung cancer (NSCLC).
- Limited data exists on neoadjuvant ICI for resectable (UICC stage III) or oligometastatic (UICC stage IVa) NSCLC.
Purpose of the Study:
- To evaluate the safety and efficacy of neoadjuvant ICI in patients with resectable or oligometastatic NSCLC.
- To assess the impact of neoadjuvant ICI on surgical procedures and oncological outcomes.
Main Methods:
- Patients with advanced or oligometastatic NSCLC and PD-L1 expression >50% received neoadjuvant ICI (pembrolizumab or atezolizumab).
- Thoracic surgical resection was performed approximately four weeks after ICI initiation.
- Comprehensive staging, tolerability, radiological and histopathological tumor response, and surgical outcomes were analyzed.
Main Results:
- Four patients (adenocarcinoma and squamous cell carcinoma) received neoadjuvant ICI without complications; surgery was not delayed.
- Partial response (PR) was observed in three patients, and stable disease (SD) in one, per iRECIST criteria.
- Complete pathological response (CPR) was achieved in two patients, with one remaining relapse-free at 12-24 months follow-up. Two patients with partial pathological response (PPR) developed distant metastasis or local recurrence.
Conclusions:
- Neoadjuvant ICI is well-tolerated and feasible in selected NSCLC patients, not negatively impacting surgical procedures.
- Complete pathological response (CPR) after neoadjuvant ICI correlates with promising oncological outcomes.
- Partial pathological response (PPR) indicates a limited prognosis, necessitating further investigation.
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