1203P - An exploratory Phase 2 study of pemetrexed (Pem) and cisplatin (Cis) as preoperative chemotherapy (CT) in the treatment of Stage IIIAN2 nonsquamous...

Date 27 September 2014
Event ESMO 2014
Session Poster Display session
Topics Anti-Cancer Agents & Biologic Therapy
Non-Small-Cell Lung Cancer, Locally Advanced
Presenter Ugo Pastorino
Citation Annals of Oncology (2014) 25 (suppl_4): iv417-iv425. 10.1093/annonc/mdu348
Authors U. Pastorino1, M. Platania2, F. Rea3, M. Schiavon3, A. Ceribelli4, A. Mussi5, V. Monica6, M. Das7, V. Soldatenkova8, C.M. Visseren-Grul9, G. Scagliotti10
  • 1Medical Oncology Department, Istituto Nazionale per lo studio e la Cura dei Tumori, 20133 - Milan/IT
  • 2Medical Oncology Department, Istituto Nazionale per lo studio e la Cura dei Tumori, Milan/IT
  • 3Chirurgia Toracica, Azienda Ospedaliera di Padova, Padova/IT
  • 4Medical Oncology A, Regina Elena Cancer Institute, Rome/IT
  • 5Chirurgia Toracica, Azienda Ospedaliera Universitaria Pisana - Ospedale di Cisanello, Pisa/IT
  • 6Department Of Oncology, University of Torino at San Luigi Gonzaga Hospital Regione Gonzole 10, Orbassano/IT
  • 7Eli Lilly Research Laboratories, Eli Lilly and Company, Erl Wood/GB
  • 8European Statistics Oncology, Lilly Deutschland GmbH, Bad Homburg/DE
  • 9Medical Oncology, Eli Lilly and Company, Houten/NL
  • 10Unità Di Oncologia Polmonare A.o., University of Torino at San Luigi Gonzaga Hospital Regione Gonzole 10, Orbassano/IT

Abstract

Aim

This study was designed to evaluate the response rate of Pem-Cis as preoperative CT in patients with stage IIIAN2 NS NSCLC. The neoadjuvant setting provided the opportunity to obtain tumor tissue samples for exploratory analyses of specific biomarkers pre and post CT.

Methods

This single arm, multicenter Phase II study evaluated 3 cycles of preoperative Pem-Cis CT followed by surgery in patients with stage IIIAN2 NS NSCLC and Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0-1. Patients received Pem 500 mg/m2 + Cis 75 mg/m2 IV on Day 1 Q3W with vitamin and dexamethasone supplementation and then underwent surgery. The primary endpoint was the overall response rate (ORR: complete response [CR] + partial response [PR]) after 3 CT cycles. A total of 33 patients were planned for enrolment. Secondary endpoints included pathological complete resection rate after surgery, tumor downstaging, and association between ORR and biomarker mRNA and protein expression (TS, TTF 1, E2F1, ERCC1, and BRCA1).

Results

Patient enrolment was stopped early due to difficulties in identifying suitable patients. Of 19 enrolled patients (median age 62 years male/female 68%/32%, ECOG PS 0/1 79%/21%, adenocarcinoma 90%), 17 (89.5%) completed CT, and 15 (78.9%) completed CT and surgery. The ORR was 41.2% (95% CI: 18.4, 67.1%), all PRs. Of 17 patients with available scans 10 (58.8%) experienced tumor downstaging (stage IIIAN2 to IIIA, II, or I). Out of 15 patients undergoing surgery, 14 had a pathological complete resection resulting in a complete resection rate of 93.3% (95% CI: 68.1, 99.8%). No new safety signals were identified. Other efficacy outcomes are still immature.

Conclusions

Pre-operative CT with Pem-Cis is active in patients with stage IIIAN2 NS NSCLC. The ORR of 41.2% is consistent with previous reports in this patient population. Assessment of the associations between ORR and baseline biomarker expression is ongoing.

Disclosure

M. Das: MD is an employee and stock holder of Eli Lilly and Company; V. Soldatenkova: VS is an employee and stock holder of Eli Lilly and Company; C.M. Visseren-Grul: CVG is an employee and stock holder of Eli Lilly and Company; G. Scagliotti: GS has participated on advisory boards for Eli Lilly and Company, Astra Zeneca, Pfizer, and Roche. All other authors have declared no conflicts of interest.