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129PD A SWISS RETROSPECTIVE LUNG CANCER SURVEY ON DOSE CHANGE AND DURATION OF TREATMENT WITH ORAL TYROSINE KINASE INHIBITORS (TKI)
Advanced NSCLC
S55
129PD A SWISS RETROSPECTIVE LUNG CANCER SURVEY ON DOSE CHANGE AND DURATION OF TREATMENT WITH ORAL TYROSINE KINASE INHIBITORS (TKI) R. Cathomas1 , A. von Rohr2 , P. H¨ osli3 , M. Giger4 , S. Malz5 , D. Betticher6 1 Medical Oncology, Kantonsspital Graub¨ unden, Chur, Switzerland, 2 Onkologie, Onkozentrum Hirslanden, Z¨ urich, Switzerland, 3 Oncology, Rue Entremous 11, Yverdon-les-Bains, Switzerland, 4 Oncology, Spital Rorschach, Rorschach, Switzerland, 5 Oncology, Roche Phrama Schweiz AG, Reinach, Switzerland, 6 Clinique de M´ edicine, Hˆ opital Cantonal Fribourg, Fribourg, Switzerland Background: There are only limited data available which reflect dose modifications of oral EGFR-TKI such as erlotinib (Tarceva® ) in daily practice. The main objectives of this survey were to characterize changes in dosing during the course of treatment and identify factors which influence the duration of therapy. Methods: A retrospective post-marketing survey was conducted at 12 sites in Switzerland between May 2007 and April 2008. Patients (pts) who were treated with an oral TKI as 2nd or 3rd line therapy for NSCLC were included. Information was collected on pts characteristics, treatment dose and duration and rating of therapy success. Symptomatic improvement was documented on a yes/no basis. Results: A total of 53 pts were included; 52 received erlotinib. Patients characteristics are listed in table 1. One third of the pts had a dose reduction (23%) or dose delay (10%). Most common reasons for dose reduction/delay were rash (71%) and/or diarrhea (43%). 54% of pts with dose change and 27% of pts with no dose change were rated as having derived a benefit from erlotinib therapy. Median duration of treatment was 80 days, with 6 pts (11.5%) treated for more than 6 months. 45% of pts who received one dose change were treated >120 days whereas 27% of pts in the group with no dose change had a treatment duration of >120 days. 6 out of 12 pts with squamous cell histology were treated >120 days. 57% (25/44) of pts experienced a symptom improvement in cough, 45% (19/42) in dyspnea and 28% (11/39) reported an improvement in pain. Patient characteristic
%
Male Current/former smoker Adenocarcinoma Squamous cell carcinoma Caucasian Age 50 70 >70 yrs 2nd line
60 71 60 23 100 50 23 51
Conclusions: This retrospective analysis shows that pts characteristics of erlotinib in clinical practice are consistent with data from clinical trials literature. A higher rate of dose reductions due to erlotinib induced rash could be observed where therapy was rated successful and in pts with long term benefit. This supports the hypothesis that treatment duration and success of erlotinib therapy in advanced NSCLC correlates with the appearance and intensity of rash.
130PD ERLOTINIB RELATED TOXICITY IN ELDERLY PATIENTS AFFECTED BY NON-SMALL CELL LUNG CANCER (NSCLC) A. Palazzo, R. Iacovelli, M. Mazzoli, M.L. Mancini, A. Passaro, A. Altavilla, D. Conte, G. Naso, E. Cortesi Experimental Medicine, Medical Oncology B, “Sapienza” University of Rome, Rome, Italy Background: Erlotinib inhibits the tyrosine kinase activity of the epidermal growth factor receptor (EGFR). No randomized studies have been reported to document the efficacy and tolerance in elderly patients (pts) treated with EGFR inhibitors. A number of age related changes in drug absorption, distribution, metabolism and excretion can contribute to differences in treatment tolerance in older patients and could predispose them to unpredictable toxicities. Methods: We performed a retrospective analysis of toxicity in elderly pts (65 y), treated at our centre for NSCLC with Erlotinib (150 mg/day) and we described the occurrence of adverse events by the following two age group of elderly: 75 y (young elderly) and >75 y (older elderly). Results: From January 2007 to December 2008, 160 pts affected by NSCLC, were treated with Erlotinib and 41 pts (25.6%) aged >65 y were valuable for toxicity. Patients characteristics were: 29 young elderly with a median age of 70.6y (range 65 75), 14 male and 15 female; 12 pts older elderly with a median age of 78.5y (range 76 87), 6 male and 6 female. Smoking status was 12.1% current, 39.1% never and 48.7% former smokers. Diagnosis was stage IV in more than 85% of all patients and histology was adenocarcinoma in 70.7%, bronchioloalveolar carcinoma in 12.2%; squamous carcinoma in 17.1%. Performance status were 1 in 46.4%, 2 in 39% and 3 in 14.6%. 75.6% pts received Erlotinib as a second line of treatment and 24.4% as a third line. For each young and older elderly group, 65.5% and 58.3% of pts reported respectively at least one adverse events of any grade. Cutaneous rush occurred in 44.8% (G1 in 10.3%, G2 in 17.2%, G3 in17.2%) and 50% (G1 in 25%, G2 in 16.6%, G3 in 8.3%), diarrhea occurred in 34.5% (G1 in 27.6%, G2 in 6.9%) and 33.3% (G1 in 25.0%, G2 in 8.3%) of pts. The ocular discomfort and fatigue was reported by 14.6% of pts, and peri-ungual toxicity by 9.7% of pts. Conclusions: These data indicate as in a population 11.5 years older than that represented in the Erlotinib BR.21 trial (Shepherd FA et al. NEJM 2005), cutaneous rush and diarrhea remain the most commonly reported toxicity. No difference was observed between young and older elderly for any grade of these adverse events and age did not represent a contraindication to therapy with Erlotinib. 131PD LAPATINIB WITH CHEMOTHERAPY IN FIRST-LINE TREATMENT OF ADVANCED NSCLC IN NEVER SMOKERS OR SELDOM SMOKERS R. Pandey, S. Dey, A. Mukhopadhyay Medical Oncology, Netaji Subhash Chandra Bose Cancer Research Institute, Kolkata, India Background: Her2 overexpression is known to be a poor prognostic marker in lung cancer. It is seen in 11 33% of Non Small Cell Lung Cancers (NSCLC). There have been case reports of response to Trastuzumab treatment in NSCLC. In addition Her2 Pathway is also implicated in a cross talk mechanism causing resistance to EGFR inhibitors. There is a good rationale to consider dual blockade of Her2 and EGFR in NSCLC in seldom or never smokers as we have learnt from our experience with Erlotinib. This study was designed to assess the efficacy of Lapatinib in NSCLC. Methods: From September 2007 to January 2008, 27 patients of metastatic NSCLC who were never or seldom smokers were randomized to receive 4 cycles of Paclitaxel and Carboplatin with or without Lapatinib. Patients were assessed for tumor
S55
129PD A SWISS RETROSPECTIVE LUNG CANCER SURVEY ON DOSE CHANGE AND DURATION OF TREATMENT WITH ORAL TYROSINE KINASE INHIBITORS (TKI) R. Cathomas1 , A. von Rohr2 , P. H¨ osli3 , M. Giger4 , S. Malz5 , D. Betticher6 1 Medical Oncology, Kantonsspital Graub¨ unden, Chur, Switzerland, 2 Onkologie, Onkozentrum Hirslanden, Z¨ urich, Switzerland, 3 Oncology, Rue Entremous 11, Yverdon-les-Bains, Switzerland, 4 Oncology, Spital Rorschach, Rorschach, Switzerland, 5 Oncology, Roche Phrama Schweiz AG, Reinach, Switzerland, 6 Clinique de M´ edicine, Hˆ opital Cantonal Fribourg, Fribourg, Switzerland Background: There are only limited data available which reflect dose modifications of oral EGFR-TKI such as erlotinib (Tarceva® ) in daily practice. The main objectives of this survey were to characterize changes in dosing during the course of treatment and identify factors which influence the duration of therapy. Methods: A retrospective post-marketing survey was conducted at 12 sites in Switzerland between May 2007 and April 2008. Patients (pts) who were treated with an oral TKI as 2nd or 3rd line therapy for NSCLC were included. Information was collected on pts characteristics, treatment dose and duration and rating of therapy success. Symptomatic improvement was documented on a yes/no basis. Results: A total of 53 pts were included; 52 received erlotinib. Patients characteristics are listed in table 1. One third of the pts had a dose reduction (23%) or dose delay (10%). Most common reasons for dose reduction/delay were rash (71%) and/or diarrhea (43%). 54% of pts with dose change and 27% of pts with no dose change were rated as having derived a benefit from erlotinib therapy. Median duration of treatment was 80 days, with 6 pts (11.5%) treated for more than 6 months. 45% of pts who received one dose change were treated >120 days whereas 27% of pts in the group with no dose change had a treatment duration of >120 days. 6 out of 12 pts with squamous cell histology were treated >120 days. 57% (25/44) of pts experienced a symptom improvement in cough, 45% (19/42) in dyspnea and 28% (11/39) reported an improvement in pain. Patient characteristic
%
Male Current/former smoker Adenocarcinoma Squamous cell carcinoma Caucasian Age 50 70 >70 yrs 2nd line
60 71 60 23 100 50 23 51
Conclusions: This retrospective analysis shows that pts characteristics of erlotinib in clinical practice are consistent with data from clinical trials literature. A higher rate of dose reductions due to erlotinib induced rash could be observed where therapy was rated successful and in pts with long term benefit. This supports the hypothesis that treatment duration and success of erlotinib therapy in advanced NSCLC correlates with the appearance and intensity of rash.
130PD ERLOTINIB RELATED TOXICITY IN ELDERLY PATIENTS AFFECTED BY NON-SMALL CELL LUNG CANCER (NSCLC) A. Palazzo, R. Iacovelli, M. Mazzoli, M.L. Mancini, A. Passaro, A. Altavilla, D. Conte, G. Naso, E. Cortesi Experimental Medicine, Medical Oncology B, “Sapienza” University of Rome, Rome, Italy Background: Erlotinib inhibits the tyrosine kinase activity of the epidermal growth factor receptor (EGFR). No randomized studies have been reported to document the efficacy and tolerance in elderly patients (pts) treated with EGFR inhibitors. A number of age related changes in drug absorption, distribution, metabolism and excretion can contribute to differences in treatment tolerance in older patients and could predispose them to unpredictable toxicities. Methods: We performed a retrospective analysis of toxicity in elderly pts (65 y), treated at our centre for NSCLC with Erlotinib (150 mg/day) and we described the occurrence of adverse events by the following two age group of elderly: 75 y (young elderly) and >75 y (older elderly). Results: From January 2007 to December 2008, 160 pts affected by NSCLC, were treated with Erlotinib and 41 pts (25.6%) aged >65 y were valuable for toxicity. Patients characteristics were: 29 young elderly with a median age of 70.6y (range 65 75), 14 male and 15 female; 12 pts older elderly with a median age of 78.5y (range 76 87), 6 male and 6 female. Smoking status was 12.1% current, 39.1% never and 48.7% former smokers. Diagnosis was stage IV in more than 85% of all patients and histology was adenocarcinoma in 70.7%, bronchioloalveolar carcinoma in 12.2%; squamous carcinoma in 17.1%. Performance status were 1 in 46.4%, 2 in 39% and 3 in 14.6%. 75.6% pts received Erlotinib as a second line of treatment and 24.4% as a third line. For each young and older elderly group, 65.5% and 58.3% of pts reported respectively at least one adverse events of any grade. Cutaneous rush occurred in 44.8% (G1 in 10.3%, G2 in 17.2%, G3 in17.2%) and 50% (G1 in 25%, G2 in 16.6%, G3 in 8.3%), diarrhea occurred in 34.5% (G1 in 27.6%, G2 in 6.9%) and 33.3% (G1 in 25.0%, G2 in 8.3%) of pts. The ocular discomfort and fatigue was reported by 14.6% of pts, and peri-ungual toxicity by 9.7% of pts. Conclusions: These data indicate as in a population 11.5 years older than that represented in the Erlotinib BR.21 trial (Shepherd FA et al. NEJM 2005), cutaneous rush and diarrhea remain the most commonly reported toxicity. No difference was observed between young and older elderly for any grade of these adverse events and age did not represent a contraindication to therapy with Erlotinib. 131PD LAPATINIB WITH CHEMOTHERAPY IN FIRST-LINE TREATMENT OF ADVANCED NSCLC IN NEVER SMOKERS OR SELDOM SMOKERS R. Pandey, S. Dey, A. Mukhopadhyay Medical Oncology, Netaji Subhash Chandra Bose Cancer Research Institute, Kolkata, India Background: Her2 overexpression is known to be a poor prognostic marker in lung cancer. It is seen in 11 33% of Non Small Cell Lung Cancers (NSCLC). There have been case reports of response to Trastuzumab treatment in NSCLC. In addition Her2 Pathway is also implicated in a cross talk mechanism causing resistance to EGFR inhibitors. There is a good rationale to consider dual blockade of Her2 and EGFR in NSCLC in seldom or never smokers as we have learnt from our experience with Erlotinib. This study was designed to assess the efficacy of Lapatinib in NSCLC. Methods: From September 2007 to January 2008, 27 patients of metastatic NSCLC who were never or seldom smokers were randomized to receive 4 cycles of Paclitaxel and Carboplatin with or without Lapatinib. Patients were assessed for tumor