Pathologic responses in oligometastatic NSCLC patients treated with neoadjuvant immune checkpoint blockade with and
Tobias Boch1, Nikolaj Frost2, Linna Sommer3
1DKFZ-Hector Cancer Institute at the University Medical Center Mannheim, Mannheim, Germany; Division of Personalized Medical Oncology (A420), German Cancer Research Center (DKFZ), Heidelberg, Germany; Department of Personalized Oncology, University Hospital Mannheim, Medical Faculty Mannheim, University of Heidelberg, Mannheim, Germany.
Objectives:
Immune checkpoint inhibitors (ICI) have significantly improved outcome of patients with advanced NSCLC and recently also showed benefit in early-stage disease. Patients with oligometastatic disease (OMD) harbor limited metastases, resectable primary tumors and derive benefit from treatment with multimodal locally ablative and systemic therapy approaches. Nothing is known about feasibility and efficacy of neoadjuvant ICI in this setting.
Material And Methods:
We here provide data from a multicenter retrospective study comprising 13 patients with NSCLC and OMD (≤3 distant metastases) from 5 university medical centers in Germany who have been treated with neoadjuvant ICI alone (n = 4) or in combination with chemotherapy (CT) (n = 9) prior to resection of the primary tumor. We analyzed complete (pCR) and major pathological remission (MPR) rates.
Results:
These data show that neoadjuvant immunotherapy applied mostly in combination with CT results in high rates of pCR and MPR (54 and 69%, respectively). Up to now, 85% of patients are free of progression with a median follow-up of 9 months (3-28 months). Single cell RNASeq analysis of tumor tissue from one patient treated with CT-ICI indicates a strong predominance of adaptive immune cell populations over a small minority of epithelial (tumor) cells.
Conclusion:
Neoadjuvant ICI with or without CT is a promising therapeutic concept in patients with OMD.
Insights
Neoadjuvant immune checkpoint inhibitors (ICI) show promise for non-small cell lung cancer (NSCLC) with oligometastatic disease (OMD). This approach, often combined with chemotherapy, achieved high pathological remission rates and maintained progression-free survival in early trials.
Area of Science:
- Oncology
- Immunotherapy
- Thoracic Surgery
Background:
- Immune checkpoint inhibitors (ICI) have transformed outcomes in advanced non-small cell lung cancer (NSCLC) and early-stage disease.
- Oligometastatic disease (OMD) involves limited metastases with resectable primary tumors, benefiting from multimodal therapy.
- The efficacy and feasibility of neoadjuvant ICI in NSCLC with OMD remain largely unexplored.
Purpose of the Study:
- To evaluate the feasibility and efficacy of neoadjuvant ICI in patients with NSCLC and OMD.
- To assess pathological remission rates (complete and major) following neoadjuvant ICI treatment.
- To analyze progression-free survival in this patient cohort.
Main Methods:
- A multicenter retrospective study involving 13 patients with NSCLC and OMD (≤3 distant metastases).
- Patients received neoadjuvant ICI alone (n=4) or combined with chemotherapy (CT) (n=9) before primary tumor resection.
- Pathological remission rates (pCR and MPR) were analyzed.
Main Results:
- Neoadjuvant immunotherapy, predominantly with CT, yielded high pCR (54%) and MPR (69%) rates.
- 85% of patients remained progression-free at a median follow-up of 9 months (range: 3-28 months).
- Single-cell RNA sequencing indicated a strong adaptive immune cell presence post-treatment.
Conclusions:
- Neoadjuvant ICI, with or without CT, represents a promising therapeutic strategy for NSCLC patients with OMD.
- This approach demonstrates encouraging pathological response and disease control.
- Further investigation is warranted to confirm these findings in larger cohorts.
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