EGFR TKIs
Front-line erlotinib in unselected patients with advanced NSCLC and poor performance status - the TOPICAL study Niki Karachaliou1, Jia Wei2, Ana Daniela Marques3, Rafael Rosell1,4 1
Breakthrough Cancer Research Unit, Pangaea Biotech, Dexeus University Institute, Barcelona, Spain; 2Comprehensive Cancer Centre of Drum Tower
Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing, China; 3Medical Oncology Deartment, Hospital de Braga, Portugal; 4Catalan Institute of Oncology, Badalona, Spain Correspondence to: Dr Niki Karachaliou. Breakthrough Cancer Research Unit, Pangaea Biotech, Dexeus University Institute, Sabino Arana 5-19, 08028 Barcelona, Spain. Email: [email protected]. Submitted Oct 06, 2012. Accepted for publication Nov 08, 2012. doi: 10.3978/j.issn.2218-6751.2012.11.04 Scan to your mobile device or view this article at: http://www.tlcr.org/article/view/628/1410
Lung cancer has long been recognized as an extremely heterogeneous disease since its development, in terms of clinical characterizations, prognosis, response and tolerance to treatment, is unique in every patient. Eastern Cooperative Oncology Group performance status (ECOG PS) is the most important predictor of outcome in advanced nonsmall-cell lung cancer (NSCLC). Patients with PS ≥2 tend to tolerate treatment poorly and have significantly inferior survival compared with patients with PS 0 to 1 (1). As a result, patients with poor PS have historically been excluded from clinical trials, and scant evidence-based information is available to guide clinical practice. Studies evaluating the safety and efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, such as erlotinib and gefitinib, have given rise to a remarkable degree of optimism based on prolonged remissions and improvements in quality of life in small numbers of patients whose condition no longer responded to standard chemotherapy (2,3). The Lancet Oncology has featured this month the results of the TOPICAL trial, a double-blind, placebo-controlled phase III trial which investigated the use of erlotinib in NSCLC patients with poor PS and several co-morbidities (4). Seventy eight centers in the UK participated, and a total of 670 chemotherapy naïve patients with newly diagnosed, pathologically confirmed stage IIIB or IV NSCLC were involved (4). Patients were randomized to receive either erlotinib, 150 mg per day, or placebo until disease progression or unacceptable toxicity (4). The primary endpoint was overall survival. The trial began enrolling patients in 2005 and, as a result, EGFR mutation status was not used as an enrolment criterion (4). Patients were
required to have been deemed unsuitable for chemotherapy because of poor PS (≥2), or the presence of several comorbidities, or both, and have estimated life expectancy of at least 8 weeks (4). Median overall survival did not improve with the use of erlotinib compared to placebo [erlotinib, 3.7 months, 95% CI, 3.2-4.2, vs. placebo, 3.6 months, 95% CI, 3.2-3.9; unadjusted hazard ratio (HR) 0.94, 95% CI, 0.81-1.10, P=0.46] (4). Adverse events reported showed that grade 3 or 4 diarrhea was more common with erlotinib than placebo [8% (28 of 334) vs. 1% (4 of 313), P=0.0001], as was highgrade rash [23% (79 of 334) vs. 2% (5 of 313), P
Front-line erlotinib in unselected patients with advanced NSCLC and poor performance status - the TOPICAL study Niki Karachaliou1, Jia Wei2, Ana Daniela Marques3, Rafael Rosell1,4 1
Breakthrough Cancer Research Unit, Pangaea Biotech, Dexeus University Institute, Barcelona, Spain; 2Comprehensive Cancer Centre of Drum Tower
Hospital, Medical School of Nanjing University, Clinical Cancer Institute of Nanjing University, Nanjing, China; 3Medical Oncology Deartment, Hospital de Braga, Portugal; 4Catalan Institute of Oncology, Badalona, Spain Correspondence to: Dr Niki Karachaliou. Breakthrough Cancer Research Unit, Pangaea Biotech, Dexeus University Institute, Sabino Arana 5-19, 08028 Barcelona, Spain. Email: [email protected]. Submitted Oct 06, 2012. Accepted for publication Nov 08, 2012. doi: 10.3978/j.issn.2218-6751.2012.11.04 Scan to your mobile device or view this article at: http://www.tlcr.org/article/view/628/1410
Lung cancer has long been recognized as an extremely heterogeneous disease since its development, in terms of clinical characterizations, prognosis, response and tolerance to treatment, is unique in every patient. Eastern Cooperative Oncology Group performance status (ECOG PS) is the most important predictor of outcome in advanced nonsmall-cell lung cancer (NSCLC). Patients with PS ≥2 tend to tolerate treatment poorly and have significantly inferior survival compared with patients with PS 0 to 1 (1). As a result, patients with poor PS have historically been excluded from clinical trials, and scant evidence-based information is available to guide clinical practice. Studies evaluating the safety and efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors, such as erlotinib and gefitinib, have given rise to a remarkable degree of optimism based on prolonged remissions and improvements in quality of life in small numbers of patients whose condition no longer responded to standard chemotherapy (2,3). The Lancet Oncology has featured this month the results of the TOPICAL trial, a double-blind, placebo-controlled phase III trial which investigated the use of erlotinib in NSCLC patients with poor PS and several co-morbidities (4). Seventy eight centers in the UK participated, and a total of 670 chemotherapy naïve patients with newly diagnosed, pathologically confirmed stage IIIB or IV NSCLC were involved (4). Patients were randomized to receive either erlotinib, 150 mg per day, or placebo until disease progression or unacceptable toxicity (4). The primary endpoint was overall survival. The trial began enrolling patients in 2005 and, as a result, EGFR mutation status was not used as an enrolment criterion (4). Patients were
required to have been deemed unsuitable for chemotherapy because of poor PS (≥2), or the presence of several comorbidities, or both, and have estimated life expectancy of at least 8 weeks (4). Median overall survival did not improve with the use of erlotinib compared to placebo [erlotinib, 3.7 months, 95% CI, 3.2-4.2, vs. placebo, 3.6 months, 95% CI, 3.2-3.9; unadjusted hazard ratio (HR) 0.94, 95% CI, 0.81-1.10, P=0.46] (4). Adverse events reported showed that grade 3 or 4 diarrhea was more common with erlotinib than placebo [8% (28 of 334) vs. 1% (4 of 313), P=0.0001], as was highgrade rash [23% (79 of 334) vs. 2% (5 of 313), P
