Abstract 429P
Background
The optimal systemic treatment for patients (pts) with stage IV large cell neuroendocrine carcinoma (LCNEC) is unknown and the overall survival (OS) is poor. Here, we describe current treatment patterns and clinical outcomes of pts with stage IV LCNEC, including stratification by immunohistochemical (IHC) protein retinoblastoma 1 (pRb) status.
Methods
From the Netherlands Cancer Registry (NCR), clinical data were obtained from all pts with LCNEC diagnosed between 2019 and 2022. In addition, the nationwide Netherlands Pathology Registry was searched for NSCLC ‘not otherwise specified’ (NOS)—with ≥2 positive neuroendocrine (NE) markers—and clinical data were retrieved from the NCR. Central pathology reviewand IHC pRb staining were performed when tumour material was available. OS was calculated from time of diagnosis of stage IV until death/censored at last OS update in April 2024.
Results
In total 530 pts were identified, of whom 269 (51%) real-world stage IV pts received systemic treatment. 132 were eligible for central pathology review. In 88/132 (67%) the diagnosis LCNEC was confirmed. Panel-reviewed non-LCNEC diagnoses (n=44) included SCLC (34%) and NSCLC NOS (34%). Pts treated with chemo-immunotherapy (CTx-IO) outperformed those receiving chemotherapy alone (CTx) in both real-world data (p < 0.001) and the combined cohort of pts with panel-reviewed LCNEC and non-LCNEC p=0.02). This was not observed in pts with panel-reviewed LCNEC. In the combined cohort of pts with panel-reviewed LCNEC and non-LCNEC, pRb retention was associated with lower risk of death for those treated with CTx-IO compared to CTx (p=0.03).
Table 429P| Cohort | Median OS | HR | |
| CTx-1O | CTx | ||
| Real-world (n=269) | 10.7 months (95% CI 9.2–15.9) | 6.7 months (95% CI 6.2–8.7) | 0.53 (95% CI 0.4–0.72) |
| Panel-reviewed (n=132) | 10.3 months (95% CI 9–18.6) | 7.6 months (95% CI 6.3–9.9) | 0.6 (95% CI 0.38–0.93) |
| Panel-reviewed LCNEC (n=88) | 9.6 months (95% CI 8.3–14.9) | 6.5 months (95% CI 5.3–8.5) | 0.71 (95% CI 0.42–1.2) |
Conclusions
Half of patients with stage IV LCNEC do not receive systemic treatment. In real-world setting, CTx-IO outperformed CTx. After central pathology review, CTx-IO was also associated with lower risk of death in the combined cohort of pts with panel-reviewed LCNEC and non-LCNEC, and in pts with retained pRb within this combined cohort.
Funding
KWF.
Disclosure
E. Speel: Financial Interests, Institutional, Research Grant: Bayer, Pfizer; Financial Interests, Institutional, Other, Patents plannend, issued or pending: AstraZeneca, GSK, Janssen, Merck. J. von der Thüsen: Financial Interests, Personal, Invited Speaker: Eli Lilly, MSD, BMS; Financial Interests, Institutional, Funding: Roche Diagnostics; Non-Financial Interests, Personal, Advisory Role: ESP, EORTC, IASLC; Non-Financial Interests, Personal, Leadership Role: BDIAP. A.C. Dingemans: Financial Interests, Institutional, Advisory Board: Roche, Amgen, Bayer, AstraZeneca, Boehringer Ingelheim, Johnson & Johnson, Boehringer Ingelheim, Pfizer, MSD; Financial Interests, Institutional, Invited Speaker: Lilly, Eli Lilly, Lilly, Amgen, Daiichi Sankyo, Roche, Roche, JNJ, Mirati, Bayer, Eli Lilly, Amgen; Financial Interests, Institutional, Other, IDMC: Roche; Financial Interests, Institutional, Expert Testimony: Mirati; Financial Interests, Institutional, Research Grant: Amgen; Non-Financial Interests, Personal, Other, Chair EORTC lung cancer group: EORTC; Non-Financial Interests, Personal, Member: IASLC, ASCO, AACR, ERS. All other authors have declared no conflicts of interest.