Bevacizumab and Erlotinib: A Promising New Approach to the Treatment of Advanced NSCLC

Abstract

Biologic agents that target molecules involved in tumor growth, progression, and pathological angiogenesis—such as the human epidermal growth factor receptor (EGFR) and vascular endothelial growth factor (VEGF)—have demonstrated efficacy in patients with non‐small cell lung cancer (NSCLC). Erlotinib (Tarceva®; OSI Pharmaceuticals, Inc., Melville, NY, Genentech, Inc., South San Francisco, CA, and F. Hoffmann‐La Roche Ltd, Basel, Switzerland), a highly selective tyrosine kinase inhibitor that inhibits EGFR, and bevacizumab (Avastin®; Genentech, Inc., South San Francisco, CA, and F. Hoffmann‐La Roche Ltd, Basel, Switzerland), a VEGF‐targeted recombinant humanized monoclonal antibody, have displayed very encouraging activity in a randomized phase II trial in patients with previously treated NSCLC. Because erlotinib and bevacizumab act on two different pathways critical to tumor growth and dissemination, administering these drugs concomitantly may confer additional clinical benefits to cancer patients with advanced disease, by virtue of their complementary (or additive) antitumor activity. The combination of bevacizumab plus erlotinib may prove to be a viable second‐line alternative to chemotherapy or erlotinib monotherapy in patients with NSCLC. The benefits of the combination may be further enhanced by selecting for patients who are likely to respond to this therapy. While a number of potential predictive markers have been identified for erlotinib, their value remains to be confirmed in prospective trials. In addition, the application of such personalized therapy will also depend on the availability of validated screening methods.

Paclitaxel/Carboplatin plus Bevacizumab/Erlotinib in the First-Line Treatment of Patients with Carcinoma of Unknown Primary Site

“…In addition, VEGF blockade appears to prevent the development of resistance to EGFR inhibition [24]. Clinically, the combination of bevacizumab and erlotinib is well tolerated and it has shown activity in several malignancies [9,25,26]. We chose to incorporate agents inhibiting both the VEGF and EGFR pathways based on our previous demonstration of the activity of the bevacizumab-erlotinib combination in the second-line treatment of CUP patients [9].…”

Napsin A and thyroid transcription factor-1 expression in carcinomas of the lung, breast, pancreas, colon, kidney, thyroid, and malignant mesothelioma

“…Although IHC has been routinely used for separating metastatic tumors from primary lung cancers especially in patients with no known primary tumors, it is also becoming more important in the classification of primary lung tumors. Indeed, recent advances in targeted therapies (eg, tyrosine kinase inhibitors and angiogenesis inhibitors) have made the distinction between adenocarcinomas and squamous cell carcinomas of the lung even more important [9][10][11][12][13][14] because not only are tyrosine kinase inhibitors more efficacious in adenocarcinomas than in squamous cell carcinomas, but also the use of antiangiogenic modalities can be associated with life-threatening pulmonary hemorrhage in squamous cell carcinomas [9,11]. There also appears to be lack of agreement among pathologists in the subtyping of nonsmall cell lung carcinomas based on H&E-stained sections alone, with concordance rates reported as low as 81% [15,16].…”

Bevacizumab and erlotinib (BE) first-line therapy in advanced non-squamous non-small-cell lung cancer (NSCLC) (stage IIIB/IV) followed by platinum-based chemotherapy (CT) at disease progression: A multicenter phase II trial (SAKK 19/05)

“…Blocking both the EGFR and VEGF pathways may produce additive anti-tumor effects in non-mutated EGFR patients and could be a valuable first-line option for patients with advanced non-squamous NSCLC [27]. A previous phase I/II trial in patients with relapsed or refractory non-squamous NSCLC treated with BE showed promising results [14].…”