Tag: Lung Cancer: Non-Small Cell

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.

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.

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.

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.