Christian Dittrich1, Zsolt Papai-Szekely2, Nuria Vinolas3, Christer Sederholm4, Joerg T Hartmann5, Dirk Behringer6, Gbenga Kazeem7, Durisala Desaiah8, Monika I Leschinger9, Joachim von Pawel10. 1. LBI-ACR VIEnna and ACR-ITR VIEnna, Kaiser Franz Josef-Spital, Vienna, Austria. Electronic address: christian.dittrich@wienkav.at. 2. St. George Hospital of Fejér County, Szekesfehervar, Hungary. 3. Hospital Clinic I Provincial, Barcelona, Spain. 4. University Hospital, Linköping, Sweden. 5. Department of Internal Medicine II-Hematology and Medical Oncology, Kiel, Germany and Catholic Hospital Consortium Ostwestfalen, Bielefeld, Germany. 6. Clinic of Hematology and Oncology, Bochum, Germany. 7. Eli Lilly UK, Erl Wood Manor, Windlesham, Surrey, United Kingdom. 8. Eli Lilly Corporate Center, Indianapolis, USA. 9. Lilly Deutschland GmbH, Bad Homburg, Germany. 10. Asklepios Hospital München-Gauting, Gauting, Germany.
Abstract
INTRODUCTION:Pemetrexed and erlotinib have been approved as second-line monotherapy for locally advanced or metastatic non-small cell lung cancer (NSCLC). This multicentre, randomised, open-label, parallel phase II study assessed efficacy and safety of pemetrexed versus pemetrexed+erlotinib in patients with advanced non-squamous NSCLC. METHODS:NSCLC stage III-IV patients who failed one prior platinum-based chemotherapy regimen, ≥ 1 measurable lesion by Response Evaluation Criteria in Solid Tumors, and Eastern Cooperative Oncology Group performance status ≤ 2 were eligible. Patients received pemetrexed 500 mg/m(2) with vitamin B12 and folic acid q3w alone or combined with erlotinib 150 mg daily. The primary end-point was progression-free survival (PFS). Secondary end-points were overall survival (OS), time-to-treatment failure (TTTF), response and toxicity. RESULTS: Of 165 randomised non-squamous patients, 159 were treated (pemetrexed: 83; pemetrexed+erlotinib: 76). The median PFS (months; 95% CI) was 2.89 (1.94, 3.38) for pemetrexed versus 3.19 (2.86, 4.70) for pemetrexed+erlotinib (hazard ratio [HR] 0.63; 95% CI: (0.44, 0.90); P = 0.0047). The median OS (months; 95% CI) was 7.75 (5.29, 10.41) for pemetrexed versus 11.83 (8.18, 16.66) for pemetrexed+erlotinib (HR: 0.68; 95% CI: 0.46, 0.98; P = 0.019). The median TTTF (months: 95% CI) was 2.4 (1.74, 2.99) for pemetrexed versus 3.0 (2.23, 4.07) for pemetrexed+erlotinib (HR 0.64; 95% CI: 0.46, 0.89; P = 0.0034). One patient died in pemetrexed+erlotinib arm due to febrile neutropenia. Grades 3/4 drug-related toxicities (in ≥ 5% of patients) in pemetrexed/pemetrexed+erlotinib were febrile neutropenia (2.4%/10.5%), diarrhoea (1.2%/5.3%), rash (1.2%/9.2%); anaemia (6%/11.8%), leukopenia (9.6%/23.7%), neutropenia (9.6%/25.0%), and thrombocytopenia (4.8%/14.5%). CONCLUSIONS:Pemetrexed+erlotinib treatment significantly improved PFS, OS and TTTF in 2nd line non-squamous NSCLC and was associated with an increase in grade 3/4 toxicities compared with pemetrexed alone.
RCT Entities:
INTRODUCTION:Pemetrexed and erlotinib have been approved as second-line monotherapy for locally advanced or metastatic non-small cell lung cancer (NSCLC). This multicentre, randomised, open-label, parallel phase II study assessed efficacy and safety of pemetrexed versus pemetrexed+erlotinib in patients with advanced non-squamous NSCLC. METHODS:NSCLC stage III-IV patients who failed one prior platinum-based chemotherapy regimen, ≥ 1 measurable lesion by Response Evaluation Criteria in Solid Tumors, and Eastern Cooperative Oncology Group performance status ≤ 2 were eligible. Patients received pemetrexed 500 mg/m(2) with vitamin B12 and folic acid q3w alone or combined with erlotinib 150 mg daily. The primary end-point was progression-free survival (PFS). Secondary end-points were overall survival (OS), time-to-treatment failure (TTTF), response and toxicity. RESULTS: Of 165 randomised non-squamous patients, 159 were treated (pemetrexed: 83; pemetrexed+erlotinib: 76). The median PFS (months; 95% CI) was 2.89 (1.94, 3.38) for pemetrexed versus 3.19 (2.86, 4.70) for pemetrexed+erlotinib (hazard ratio [HR] 0.63; 95% CI: (0.44, 0.90); P = 0.0047). The median OS (months; 95% CI) was 7.75 (5.29, 10.41) for pemetrexed versus 11.83 (8.18, 16.66) for pemetrexed+erlotinib (HR: 0.68; 95% CI: 0.46, 0.98; P = 0.019). The median TTTF (months: 95% CI) was 2.4 (1.74, 2.99) for pemetrexed versus 3.0 (2.23, 4.07) for pemetrexed+erlotinib (HR 0.64; 95% CI: 0.46, 0.89; P = 0.0034). One patient died in pemetrexed+erlotinib arm due to febrile neutropenia. Grades 3/4 drug-related toxicities (in ≥ 5% of patients) in pemetrexed/pemetrexed+erlotinib were febrile neutropenia (2.4%/10.5%), diarrhoea (1.2%/5.3%), rash (1.2%/9.2%); anaemia (6%/11.8%), leukopenia (9.6%/23.7%), neutropenia (9.6%/25.0%), and thrombocytopenia (4.8%/14.5%). CONCLUSIONS:Pemetrexed+erlotinib treatment significantly improved PFS, OS and TTTF in 2nd line non-squamous NSCLC and was associated with an increase in grade 3/4 toxicities compared with pemetrexed alone.
Authors: Mani Keshtgarpour; Wei Seong Tan; Jack Zwanziger; Saria Awadalla; Fredrick G Langi; Arkadiusz Z Dudek Journal: Anticancer Res Date: 2016-04 Impact factor: 2.480
Authors: Mary E R O'Brien; Debashis Sarker; Jaishree Bhosle; Kiruthikah Thillai; Timothy A Yap; Martina Uttenreuther-Fischer; Karine Pemberton; Xidong Jin; Sabrina Wiebe; Johann de Bono; James Spicer Journal: Cancer Chemother Pharmacol Date: 2018-08-07 Impact factor: 3.333