IMFINZI® after Chemoradiotherapy Significantly Improves Overall Survival in Stage III NSCLC

November 8th, 2018

IMFINZI® (Durvalumab) is a selective, high-affinity, human IgG1 monoclonal antibody, that blocks the binding of Programmed Death Ligand 1 (PD-L1) to Programmed Death 1 (PD-1) receptor and CD80, thereby unleashing the T cells to recognize and kill tumor cells. Patients with stage III Non Small Cell Lung Cancer (NSCLC) are often treated with platinum-based doublet chemotherapy with concurrent radiation and have a median Progression Free Survival (PFS) of approximately 8 months and 5 year survival of only 15%. PACIFIC trial is a randomized, double-blind, international, phase III study in which IMFINZI® as consolidation therapy was compared with placebo, in patients with stage III, locally advanced, unresectable NSCLC, that had not progressed following platinum-based chemoradiotherapy.
At a median follow up of 25.2 months, the 24-month Overall Survival rate was 66.3% in the IMFINZI® group and 55.6% in the placebo group, suggesting a significantly prolonged Overall Survival with IMFINZI® when compared with placebo and a 32% reduction in the risk of death (HR for death=0.68; P=0.0025). The Overall Survival benefit with IMFINZI®, was observed across all the prespecified subgroups.
PACIFIC trial is the first study to demonstrate a survival advantage for unresectable Stage III NSCLC, supporting this regimen as the standard of care.

First Line TECENTRIQ® plus Chemotherapy in Advanced Squamous NSCLC

July 30th, 2018

Non Small Cell Lung Cancer (NSCLC) accounts for approximately 85% of all lung cancers and 30% are Squamous Cell Carcinomas (SCC). Non Small Cell Lung Cancer patients with Squamous Cell histology have been a traditionally hard- to-treat, patient group, and less than 15% of patients with advanced Squamous NSCLC survive a year after diagnosis and less than 5% of patients survive for five years or longer. IMpower131 is a multicenter, open-label, phase III study, in which 1021 chemotherapy-naïve patients with stage IV Squamous NSCLC received TECENTRIQ® ((Atezolizumab)) along with Carboplatin, and Paclitaxel, TECENTRIQ® along with Carboplatin, and ABRAXANE® (nab-paclitaxel) or Carboplatin and ABRAXANE® (control group). The addition of  TECENTRIQ® to chemotherapy significantly improved median Progression Free Survival across all PD-L1 subgroups. This is the first phase III trial of an immunotherapy-based treatment regimen, to demonstrate a significant improvement in Progression Free Survival, in advanced Squamous NSCLC.

TAGRISSO® Superior to First Generation EGFR TKIs in Advanced Non-Small Cell Lung Cancer

November 27th, 2017

Approximately 10% to 15% of Caucasian patients and 35-50% of Asian patients with Adenocarcinomas, harbor activating EGFR (Epidermal Growth Factor Receptor) mutations and 90% of these mutations are either Exon 19 deletions or L858R point mutations in Exon 21. EGFR-Tyrosine Kinase Inhibitors (TKIs) such as TARCEVA® (Erlotinib), IRESSA® (Gefitinib) and GILOTRIF® (Afatinib), have demonstrated a 60% to 70% response rate as monotherapy when administered as first line treatment, in patients with metastatic NSCLC, who harbor the sensitizing EGFR mutations. However, majority of these patients experience disease progression within 9 to 14 months. This resistance to frontline EGFR TKI therapy has been attributed to acquired T790M “gatekeeper” point mutation in EGFR, identified in 50% – 60% of patients.
TAGRISSO® (Osimertinib), is a third-generation Epidermal Growth Factor Receptor (EGFR) TKI and in a randomized, double blind, phase III clinical trial, demonstrated superior efficacy and tolerability compared to the Standard of Care, as first-line therapy in patients with advanced EGFR mutation positive NSCLC. This benefit was seen even in those with CNS metastases at study entry. These new finding are very likely to change the treatment paradigm for NSCLC patients whose tumors harbor EGFR mutations.


VERISTRAT® Testing – A novel approach to NSCLC

October 27th, 2013

VeriStrat®, a serum based proteomic assay can help physicians identify patients who are likely to have good or poor outcomes after treatment with EGFR inhibitors and thereby can provide valuable insight into whether chemotherapy or targeted therapy with TARCEVA®, a EGFR-TKI, is appropriate for their patients with advanced NSCLC, in the second line setting. This information is especially important for patients without an EGFR mutation or for those, whose EGFR mutation status is unknown. In the PROSE trial, patients classified as VeriStrat-Poor have better survival with chemotherapy than TARCEVA®, whereas patients classified as VeriStrat-Good have similar survival with TARCEVA® and chemotherapy. This data was presented at the 2013 ASCO meeting.

GILOTRIF® for EGFR mutation positive Lung Cancer

July 14th, 2013

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.

Oncoprescribe Blog: Nab-Paclitaxel in Non Small Cell Lung Cancer

November 23rd, 2010

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

November 4th, 2010

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

October 29th, 2010

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: Bevacizumab and CNS metastases

October 19th, 2010

The role of Bevacizumab in combination with chemotherapy for patients with advanced Non Small Cell Lung Cancer is well established. However the safety of Bevacizumab in this patient population with brain metastases has been unclear with the potential risk of CNS bleed. This issue was addressed in the PASSPORT trial which enrolled nonsquamous histology Non Small Cell Lung Cancer patients with treated brain metastases. The addition of bevacizumab to conventional chemotherapy or erlotinib in this trial was associated with a low incidence of CNS bleed suggesting that bevacizumab could be safely given for patients with Non Small Cell Lung Cancer with treated brain metastases.

Oncoprescribe Blog: Pemetrexed (Alimta) Maintenance

September 18th, 2009

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.