Rash as a Surrogate Marker for Efficacy of Epidermal Growth Factor Receptor Inhibitors in Lung Cancer

Pérez-Soler, Román

doi:10.3816/clc.2006.s.008

Cited by 93 publications

(64 citation statements)

References 34 publications

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“…Patients with advanced pancreatic cancer who experienced grade 2 rash or higher (n ϭ 102) had a reported median survival time of 10.5 months and a 1-year survival rate of 43%. A similar observation has been reported in patients with NSCLC treated with erlotinib or gefitinib (Iressa; AstraZeneca Pharmaceuticals, LP, Macclesfield, UK) and in colon cancer patients treated with cetuximab (Erbitux ® ; ImClone Systems, Inc., New York) [52][53][54]. This cannot be explained by patients who stay on treatment longer being at greater risk for rash, but may be an indication of interpatient variability in drug absorption or metabolism, or the strength of the immune system [29].…”

Section: Erlotinibmentioning

confidence: 57%

New Therapeutic Directions for Advanced Pancreatic Cancer: Targeting the Epidermal Growth Factor and Vascular Endothelial Growth Factor Pathways

Burris

Rocha-Lima

2008

The Oncologist

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After completing this course, the reader will be able to:1. Evaluate the existing chemotherapeutic options for advanced pancreatic cancer.2. Interpret data from trials of HER-1/EGFR-and VEGFR-targeted agents in advanced pancreatic cancer.3. Take advantage of the potential of biomarkers in selecting optimal molecular-targeted therapies for advanced pancreatic cancer.Access and take the CME test online and receive 1 AMA PRA Category 1 Credit ™ at CME.TheOncologist.com CME CME ABSTRACT

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Section: Erlotinibmentioning

confidence: 57%

New Therapeutic Directions for Advanced Pancreatic Cancer: Targeting the Epidermal Growth Factor and Vascular Endothelial Growth Factor Pathways

Burris

Rocha-Lima

2008

The Oncologist

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“…This correlation between rash and efficacy also appears, in an unplanned retrospective analysis, to have been an important predictive factor in the pivotal phase III trial of erlotinib in previously treated patients with advanced NSCLC. Patients who developed a rash (75%) had a significantly longer survival time than those who did not: 8.5 months for patients with grade 1 rash and 19.6 months for patients with grade 2 or 3 rash, versus 1.5 months for patients who did not develop any rash (p Ͻ .0001) [43]. Phase II trials of cetuximab in CRC, HNSCC, pancre- atic cancer, and NSCLC have also shown that patients who develop rash live longer than those who do not [44,45].…”

Section: Egfri Efficacy and Association With Severity Of Skin Rashmentioning

confidence: 93%

Epidermal Growth Factor Receptor Inhibitor–Associated Cutaneous Toxicities: An Evolving Paradigm in Clinical Management

et al. 2007

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Epidermal growth factor receptor inhibitors (EGFRIs)have demonstrated improved overall survival in patients with non-small cell lung cancer, pancreatic cancer, and colorectal cancer; however, their use is associated with dermatologic reactions of varying severity. The similar spectrum of events observed with monoclonal antibodies and tyrosine kinase inhibitors suggests such toxicities are a class effect. While such reactions do not necessarily require any alteration in EGFRI treatment, being best addressed through symptomatic treatment, there is limited evidence on which to base such therapies. In October 2006, at an international and interdisciplinary EGFRI dermatologic toxicity forum, the underlying mechanisms of these toxicities were discussed and commonly used therapeutic interventions were evaluated. Our aim was to reach a current consensus on management strategies. A three-tiered, EGFRIfocused toxicity grading system is suggested for the purposes of therapeutic decision making, and as a framework on which to build a stepwise approach to intervention. This approach to successful management is specifically tailored to accurately categorize dermatologic toxicity associated with EGFRIs, and can be easily applied by all health care professionals. The goal is to maximize quality of life in patients who are being treated with these agents-many of whom will be on these drugs for several months or even years. The Oncologist 2007;12:610 -621 Disclosure of potential conflicts of interest is found at the end of this article.

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“…Rates of discontinuation due to toxicity were 13% for lapatinib (this study) and 5% for both erlotinib (37) and gefitinib (35) when used to treat NSCLC. It remains possible that higher doses of lapatinib could achieve clinical activity through EGFR inhibition, as the severity of skin rash seen with lapatinib seems to be mild compared with that seen with other EGFR inhibitors, and skin rash has been suggested as a predictor of response to erlotinib and gefitinib (47).…”

Section: Discussionmentioning

confidence: 99%

Randomized Phase II Multicenter Trial of Two Schedules of Lapatinib as First- or Second-Line Monotherapy in Patients with Advanced or Metastatic Non–Small Cell Lung Cancer

Ross

Blumenschein

Aisner

et al. 2010

Clinical Cancer Research

110

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Purpose: This randomized phase II study was initially designed to test the activity of two dose schedules of lapatinib (GW572016H), an oral, reversible, dual tyrosine kinase inhibitor of epidermal growth factor receptor (EGFR) and human EGFR-2 (HER2/neu; HER2), in chemotherapy-naive patients with non-small cell lung cancer (NSCLC); it was later amended to target patients with bronchioloalveolar carcinoma or no smoking history.Experimental Design: Patients with good performance status and recurrent or metastatic NSCLC were randomized to lapatinib (orally, 1,500 mg once daily or 500 mg twice daily) until progression or intolerance. Patients could have had a maximum of one prior systemic therapy (chemotherapy or biological therapy) for NSCLC. Safety and activity were assessed every 4 and 8 weeks, respectively. Tumors were analyzed for EGFR and HER2 mutations and/or amplifications.Results: Of 75 patients in the nontargeted population, 1 (1.3%) had partial response and 16 (21%) had stable disease of ≥24 weeks. No complete or partial responses were observed in 56 patients in the targeted population; 14 (25%) had stable disease of ≥24 weeks. No responses were seen in three patients with EGFR mutations and five with EGFR gene amplification. No mutations in HER2 were found. One of two patients with HER2 amplification had a 51% decrease in tumor size; however, this response was unconfirmed. The most common adverse events were grade 1 or 2 diarrhea, rash, fatigue, nausea, and anorexia. Adverse events were similar across dosing regimens.Conclusions: Lapatinib was well tolerated, with no notable difference in toxicity between treatment groups. Lapatinib monotherapy did not induce a significant number of tumor regressions in NSCLC. Further studies may be warranted to determine whether lapatinib is active in combination with other agents in the treatment of NSCLC. Clin Cancer Res; 16(6); 1938-49. ©2010 AACR.Lung cancer is the leading cause of cancer-related deaths worldwide, with an estimated incidence of 1.35 million cases resulting in 1.2 million deaths annually (1). With advances in the treatment of newly diagnosed advanced non-small cell lung cancer (NSCLC), survival in patients able to receive chemotherapy has improved modestly over the past 2 decades (2). Platinum-based chemotherapy offers an initial response rate of 15% to 30%, with a median survival of 8 to 14 months. Approximately 35% to 50% of patients with good performance status will survive 1 year, although only 15% to 20% of patients survive 2 years from initial diagnosis (3-5). Targeted agents such as bevacizumab may add efficacy in selected patients at the cost of additional toxicity (6). Current strategies for drug design are focused on molecular mechanisms of tumorigenesis, such as the activation of protein kinases by somatic mutation or amplification.

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Rash as a Surrogate Marker for Efficacy of Epidermal Growth Factor Receptor Inhibitors in Lung Cancer

Cited by 93 publications

References 34 publications

New Therapeutic Directions for Advanced Pancreatic Cancer: Targeting the Epidermal Growth Factor and Vascular Endothelial Growth Factor Pathways

New Therapeutic Directions for Advanced Pancreatic Cancer: Targeting the Epidermal Growth Factor and Vascular Endothelial Growth Factor Pathways

Epidermal Growth Factor Receptor Inhibitor–Associated Cutaneous Toxicities: An Evolving Paradigm in Clinical Management

Randomized Phase II Multicenter Trial of Two Schedules of Lapatinib as First- or Second-Line Monotherapy in Patients with Advanced or Metastatic Non–Small Cell Lung Cancer

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