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.
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: 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
Results of a randomized, phase III trial of nab-paclitaxel (nab-P) and carboplatin (C) compared with cremophor-based paclitaxel (P) and carboplatin as first-line therapy in advanced non-small cell lung cancer (NSCLC)
SUMMARY: In this randomized phase III trial, the efficacy of nab-paclitaxel (ABRAXANE®) and carboplatin was compared with paclitaxel and carboplatin in advanced NSCLC of all histologic types. Patients enrolled were chemonaïve, with stage IIIb and stage IV non small cell lung cancer. Five hundred and twenty one (521) received ABRAXANE® without any premedications at 100 mg/m2 on days 1, 8 and 15 along with carboplatin given on day 1 at an AUC of 6. The control group of 525 patients received standard Paclitaxel 200mg/m2 and carboplatin at an AUC of 6 on day 1. The primary end point was overall response rate. The ABRAXANE® group had a response rate of 33% compared to 25% for the standard paclitaxel group. When broken down by histology, the response rates in those with squamous cell carcinoma was 41% in the ABRAXANE® group versus 24% in the standard paclitaxel arm and the non squamous subtypes had a response rate of 26% versus 25% in the ABRAXANE® and paclitaxel group respectively. It is hypothesized that the superior response rates in squamous cell histology may be due to the overexpression by this sub type of an albumin receptor called Caveolin–1. ABRAXANE® which is an albumin bound paclitaxel utilizes the albumin receptor Caveolin-1 (CAV1) pathway and thereby may achieve a higher intratumoral drug concentration. J Clin Oncol 28:18s, 2010 (suppl; abstr LBA7511)
Oncoprescribe Blog Nab-Paclitaxel in Non Small Cell Lung Cancer
A randomized phase III trial data was presented at ASCO 2010 by Dr. Socinski and colleagues, involving chemonaïve patients with stage IIIb and stage IV non small cell lung cancer patients. Five hundred and twenty five (525) patients received Nab-Paclitaxel (Abraxane) without any pre medications at 100 mg/m2 on days 1, 8 and 15 along with Carboplatin given on day 1 at an AUC of 6. The control group of 525 patients received standard Paclitaxel 200mg/m2 and Carboplatin at an AUC of 6 on day 1. The major end point was response rate. The Nab-Paclitaxel group had a response rate of 33% compared to 25% for the standard Paclitaxel group. When broken down by histology, the response rates in those with squamous cell carcinoma was 41% in the Nab-Paclitaxel group versus 24% in the standard Paclitaxel arm whereas the non squamous subtypes had a response rate of 26% versus 25% in the Nab-Paclitaxel and Paclitaxel group respectively. It is hypothesized that the superior response rates in squamous cell histology may be due to the overexpression by this sub type of Caveolin–1, which is a protein which may facilitate a higher intratumoral drug concentration.
So, here is something for squamous cell histology. Choosing therapy based on histology is here to stay.
Oncoprescribe Blog Predicting Chemotherapy Benefit Using Tumor Gene Expression Signature In NSCLC
A recently published article in JCO is a boost to personalized treatment in Non Small Cell Lung Cancer (NSCLC). A 15-gene expression signature derived from NSCLC tumor was able to predict survival after adjuvant chemotherapy with cisplatin and vinorelbine in patients with stage IB to II NSCLC. This study was done on tumors derived from cohort of patients in the JBR.10 trial where patients received adjuvant cisplatin and vinorelbine. Even though the survival predictability was specific for cisplatin and vinorelbine chemotherapy regimen with this 15-gene signature, one could anticipate the discovery of other tumor mRNA expression signatures for different chemotherapy regimens in the very near future. The ability to predict who will most likely benefit from adjuvant chemotherapy in NSCLC is reminiscent of the developments seen breast and colon cancer.
Oncoprescribe Blog ALK inhibitors in NSCLC – Refining individualized therapy
The therapeutic target of interest is an aberrant fusion gene, EML4-ALK. EML4 (echinoderm microtubule-associated protein-like4) – 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.
Oncoprescribe Blog Pemetrexed (Alimta) Maintenance
The survival benefit with the use of Pemetrexed (Alimta) Maintenance is intriguing and maybe more relevant for patients with non-squamous cell histology.
Pemetrexed (Alimta®) was given as maintenance treatment following four cycles of induction with platinum based combination chemotherapy (without Pemetrexed). Pemetrexed maintenance resulted in improvement in progression free survival as well as overall survival, but these benefits were observed only in patients with non squamous histology.