1142PD - Large Cell Neuroendocrine Carcinomas (LCNEC) of the lung: Pathologic features, treatment and outcomes

Date 29 September 2014
Event ESMO 2014
Session Neuroendocrine & endocrine tumours and CUP
Topics Anti-Cancer Agents & Biologic Therapy
Neuroendocrine Cancers
Pathology/Molecular Biology
Surgery and/or Radiotherapy of Cancer
Presenter Jarushka Naidoo
Citation Annals of Oncology (2014) 25 (suppl_4): iv394-iv405. 10.1093/annonc/mdu345
Authors J. Naidoo1, M.L. Santos-Zabala2, T. Iyriboz3, K. Woo4, C.S. Sima4, J.J. Fiore1, M. Kris5, S.R. Veach5, G.J. Riely5, A. Iqbal5, S. Smith-Marrone5, I.S. Sarkaria6, L.M. Krug5, C.M. Rudin5, N. Rekhtman2, M.C. Pietanza5
  • 1Medicine, Memorial Sloan Kettering Cancer Center, 10065 - New York/US
  • 2Pathology, Memorial Sloan Kettering Cancer Center, 10065 - New York/US
  • 3Radiology, Memorial Sloan Kettering Cancer Center, 10065 - New York/US
  • 4Biostatistics, Memorial Sloan Kettering Cancer Center, 10065 - New York/US
  • 5Thoracic Oncology, Memorial Sloan-Kettering Cancer Center, New York/US
  • 6Thoracic Surgery, Memorial Sloan Kettering Cancer Center, 10065 - New York/US

Abstract

Aim

LCNEC is a rare thoracic malignancy, for which pathologic classification and optimal therapies are debated. We report the largest series of stage IV LCNECs, evaluating clinicopathologic features, treatment and survival.

Methods

Pts with stage IV LCNEC evaluated at MSKCC from 2006-2013 were identified. Clinicopathologic and treatment data were collected. Radiologic RECIST evaluation was performed for pts with existing diagnostic imaging. Pts with available tissue underwent pathology re-review to confirm diagnosis, and potentially identify features that could impact outcomes.

Results

50 pts were identified (median age: 66 years; 62% male; 88% former/current smokers). Common sites of metastasis: lymph nodes (n = 29); brain (n = 22); liver (n = 13). 34% of pts had diagnostic molecular testing with PCR-based fragment length analysis, mass spectrometry based assay for point mutation genotyping, and ALK FISH testing: 24% had KRAS mutations (mtns) (n = 4/17; G12D, n = 2; G12C, n = 1; Q61H, n = 1). No EGFR mtns or ALK rearrangements were noted. 33 pts had archived tumor at MSKCC for central pathology re-review. The diagnosis of LCNEC was confirmed in all but 2 cases, which were reclassified as SCLC and combined SCLC/LCNEC (both brain metastases), respectively. Treatment data was available on 39 pts: 77% (n = 30) received first-line platinum(plt)/etoposide. 23% (n = 9) received other regimens: plt/taxane (n = 4), plt/pemetrexed (n = 1), plt/pemetrexed/bevacizumab(bev) (n = 1), temozolomide (n = 1)/bev (n = 1), clinical trial (n = 1). Objective response rate was 32% with plt/etoposide by RECIST (95% CI: 16-52%). Median OS was 12.2mos (range: 9-19.3mos) for all pts. Karnofsky performance status <80 and LDH >250 were poor prognostic factors for OS on multivariate analysis (p < 0.05).

Conclusions

Pts with stage IV LCNEC have low response to plt/etoposide treatment and poor OS. KRAS mutations are commonly observed. Prospective studies are needed to investigate optimum therapeutic strategies.

Disclosure

All authors have declared no conflicts of interest.