SUMMARY: GILOTRIF® (Afatinib) is an oral, irreversible blocker of the ErbB family which includes EGFR (ErbB1), HER2 (ErbB2), ErbB3 and ErbB4. The approval of GILOTRIF® was based on a multi-center, international, open-label, randomized, phase III trial, in which 345 patients with Stage IIIB (wet)/IV lung adenocarcinoma, with tumors demonstrating Epidermal Growth Factor Receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations, as detected by an FDA-approved test, were enrolled in a 2:1 ratio. Patients were randomized to receive GILOTRIF® 40 mg orally once daily (n=230) or ALIMTA® (Pemetrexed)/Cisplatin (n=115) given every 21 days for up to six cycles. Patients were stratified according to EGFR mutation status (exon 19 deletion vs. exon 21 L858R vs. ‘other’) and race (Asian vs. non-Asian). The primary endpoint was Progression Free Survival (PFS). The median PFS in the GILOTRIF® group was 11.1 months and 6.9 months in the chemotherapy group (HR= 0.58, P<0.001). In patients whose tumors demonstrated EGFR mutations, the median PFS was 13.6 months in the GILOTRIF® arm and 6.9 months in the chemotherapy arm (HR= 0.47, P<0.001). Objective response rates were 56% and 23% in the GILOTRIF® and chemotherapy groups respectively (P=0.001). There was no statistically significant difference in overall survival between the two treatment groups. The most frequent adverse reactions in the GILOTRIF® group were skin rash, pruritus, stomatitis, diarrhea and decreased appetite. The authors concluded that GILOTRIF® is better than chemotherapy in the first line treatment of EGFR mutant Non Small Cell Lung Cancer patients. However, it remains to be seen if this agent is superior to TARCEVA® (Erlotinib) and IRESSA® (Gefitinib). Sequist LV, Yang JC, Yamamoto N, et al. J Clin Oncol 2013;31:3327-3334
Tag: Lung Cancer: Non-Small Cell
LUX-Lung 3 A randomized, open-label, phase III study of afatinib versus pemetrexed and cisplatin as first-line treatment for patients with advanced adenocarcinoma of the lung harboring EGFR-activating mutations
SUMMARY: GILOTRIF® (Afatinib) is an oral, irreversible blocker of the ErbB family which includes EGFR (ErbB1), HER2 (ErbB2), ErbB3 and ErbB4. The approval of GILOTRIF® was based on a multi-center, international, open-label, randomized, phase III trial, in which 345 patients with Stage IIIB (wet)/IV lung adenocarcinoma, with tumors demonstrating Epidermal Growth Factor Receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations, as detected by an FDA-approved test, were enrolled in a 2:1 ratio. Patients were randomized to receive GILOTRIF® 40 mg orally once daily (n=230) or ALIMTA® (Pemetrexed)/Cisplatin (n=115). Patients were stratified according to EGFR mutation status (exon 19 deletion vs. exon 21 L858R vs. ‘other’) and race (Asian vs. non-Asian). The primary endpoint was Progression Free Survival (PFS). The median PFS in the GILOTRIF® group was 11.1 months and 6.9 months in the chemotherapy group (HR= 0.58, P<0.001). In patients whose tumors demonstrated EGFR mutations, the median PFS was 13.6 months in the GILOTRIF® arm and 6.9 months in the chemotherapy arm (HR= 0.47, P<0.0001). Objective response rates were 50.4% and 19.1% in the GILOTRIF® and chemotherapy groups respectively. There was no statistically significant difference in overall survival between the two treatment groups. The most frequent adverse reactions in the GILOTRIF® group were skin rash, pruritus, stomatitis, diarrhea and decreased appetite. The authors concluded that GILOTRIF® is better than chemotherapy in the first line treatment of EGFR mutant Non Small Cell Lung Cancer patients. However, it remains to be seen if this agent is superior to TARCEVA® (Erlotinib) and IRESSA® (Gefitinib). Yang JC, Shuler M, Yamamoto N, et al. J Clin Oncol 2012;30(18,Suppl):abstract LBA 7500.
GILOTRIF® for EGFR mutation positive Lung Cancer
GILOTRIF® (Afatinib) is an oral, irreversible blocker of the ErbB family which includes EGFR (ErbB1), HER2 (ErbB2), ErbB3 and ErbB4. The FDA approved GILOTRIF® based on a multicenter, randomized phase III trial (LUX-Lung 3) in which GILOTRIF® trumped chemotherapy when administered to chemonaive patients with EGFR mutation positive Non Small Lung Cancer. We have yet another targeted oral agent besting chemotherapy. This is another milestone in the Lung Cancer treatment paradigm.
GILOTRIF® (Afatinib)
The FDA on July 12, 2013 approved the use of GILOTRIF® tablets for the first-line treatment of patients with metastatic Non-Small Cell Lung Cancer (NSCLC) whose tumors have Epidermal Growth Factor Receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations as detected by an FDA-approved test. The FDA also approved THERASCREEN, a test provided by QIAGEN, for the detection of EGFR exon 19 deletions or exon 21 (L858R) substitution mutations. GILOTRIF® is a product of Boehringer Ingelheim Pharmaceuticals, Inc.
TARCEVA® (Erlotinib)
TARCEVA® (Erlotinib): The FDA on May 14, 2013 approved TARCEVA® for the first-line treatment of metastatic non-small cell lung cancer (NSCLC) patients whose tumors have epidermal growth factor receptor (EGFR) exon 19 deletions or exon 21 (L858R) substitution mutations. The FDA concurrently approved the cobas EGFR Mutation Test, a companion diagnostic test for detection of these molecular abnormalities. TARCEVA has had prior FDA approval for the treatment of patients with locally advanced or metastatic NSCLC after failure of at least one prior chemotherapy regimen and for maintenance treatment of patients with locally advanced or metastatic NSCLC, whose disease has not progressed after four cycles of platinum-based first-line chemotherapy. TARCEVA® is a product of Astellas Pharma Inc.
Reduced Lung-Cancer Mortality with Low-Dose Computed Tomographic Screening
SUMMARY: The National Lung Screening Trial (NLST) enrolled 53,454 individuals at high risk for lung cancer and randomly assigned them to undergo three annual screenings with either non-contrast, low-dose CT scan (LDCT) or single-view posteroanterior chest X-ray. This study demonstrated a 20% reduction in the risk of death from lung cancer in the group of people who were screened with LDCT compared to those who were screened with chest X-ray (P=0.004). Based on this study and data, the American Cancer Society has recommended lung cancer screening for individuals 55 to 74 years of age who are in fairly good health, have at least a 30 pack-year smoking history and are either still smoking or have quit smoking within the past 15 years. If a person remains in good health, annual LDCT is continued until the age of 74. Smokers should be counseled to quit smoking. Further more, people with abnormal scans should receive appropriate care and follow up. Lung cancer screening with LDCT is presently not covered by most insurance plans. The National Lung Screening Trial Research Team. N Engl J Med 2011; 365:395-409
ALIMTA® (Pemetrexed)
> The FDA on October 17, 2012 expanded the labeling for ALIMTA® to include the results of an additional trial evaluating the safety and efficacy of ALIMTA®) for the initial treatment of patients with locally advanced or metastatic, non-squamous, non-small cell lung cancer followed by pemetrexed maintenance in patients whose disease has not progressed after four cycles of platinum and pemetrexed as first-line chemotherapy. ALIMTA® is a product of Eli Lilly and Company.
ABRAXANE® (Paclitaxel albumin-bound particles)
The FDA on October 11, 2012 approved ABRAXANE® (Paclitaxel albumin-bound particles) for use in combination with PARAPLATIN® (Carboplatin) for the initial treatment of patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) who are not candidates for curative surgery or radiation therapy. ABRAXANE® is an injectable suspension and is a product of Celgene Corporation.
LUX-Lung 3 A randomized, open-label, phase III study of afatinib versus pemetrexed and cisplatin as first-line treatment for patients with advanced adenocarcinoma of the lung harboring EGFR-activating mutations
SUMMARY: Afatinib is an oral tyrosine kinase inhibitor that irreversibly inhibits EGFR (ErbB1), HER2 (ErbB2), and ErbB4. In this study, chemo naïve patients with advanced stage adenocarcinoma of the lung (stage IIIB/IV) with EGFR mutations, were randomly assigned to receive either Afatinib or a combination of Pemetrexed and Cisplatin. Primary endpoint was progression-free survival (PFS). Treatment with Afatinib resulted in a significantly prolonged PFS compared to combination chemotherapy (median 11.1 vs 6.9 months; HR 0.58; P=0.0004). Further, patients in the Afatinib group had a higher objective response rate ((56% vs 23%; p<0.0001), as well as significant delay in symptom progression, compared to the combination chemotherapy group. Yang JC-H, Schuler MH, Yamamoto N, et al. J Clin Oncol. 2012;30(suppl; abstr LBA7500).
Anaplastic Lymphoma Kinase Inhibition in Non Small Cell Lung Cancer
SUMMARY:The therapeutic target of interest is an aberrant fusion gene, EML4-ALK. EML4 (echinoderm microtubule-associated protein-like 4) – ALK (anaplastic lymphoma kinase) is a fusion-type oncoprotein and is tyrosine kinase. This oncoprotein/tyrosine kinase is found in 2-7% of all Non Small Cell Lung Cancers (NSCLC) and is generated due to an inversion in the short arm of chromosome 2. This oncoprotein is more prevalent in patients with adenocarcinoma who have little or no exposure to tobacco. Tyrosine kinases normally play an important role in cellular proliferation and differentiation. However with point mutations, translocation/rearrangement and amplifications of their respective genes, these tyrosine kinases can potentially cause malignancy. Such is the case with mutations or translocations of the Anaplastic Lymphoma Kinase gene (ALK). In an article published in the October 28, 2010 issue of the NEJM, Crizotinib an oral small molecule tyrosine kinase inhibitor of ALK tyrosine kinase resulted in an overall response rate of 57% in patients who had progressed on prior therapies. Stable disease was noted in 33% of the patients. This is remarkable considering that the response rates in this patient population treated with second line chemotherapy is around 10-15%. As we move forward, it is very likely that genotyping patients and tailoring therapy accordingly, will become standard practice. N Engl J Med 2010; 363:1693-1703