Adding Bevacizumab to Carboplatin-Pemetrexed may Result in Modest Overall Survival Benefits in NSCLC

Researcher from the Abramson Cancer Center at University of Pennsylvania have demonstrated that adding bevacizumab (Avastin®; Genentech/Roche) to carboplatin-pemetrexed when treating patients with advanced non-squamous non-small cell lung cancer (NSCLC) results in a modest but consistent survival benefit.

The study results were published in the May 2019 issue of JNCCN—Journal of the National Comprehensive Cancer Network,

Based on a large, real-world dataset to demonstrate the researchers observed a modest but consistent survival benefit. This combination is already a common clinical practice, but there has never been a randomized prospective clinical trial to determine whether adding bevacizumab confers any survival benefit.

“Our results suggest that in patients with a contraindication to immunotherapy, such as connective tissue, rheumatologic, or interstitial lung disease, bevacizumab may be a reasonable alternative, instead of pembrolizumab, to add to carboplatin-pemetrexed ,” said lead author, Stephen J. Bagley, MD, MSCE, Assistant Professor of Hematology-Oncology, Abramson Cancer Center.

“Many oncologists were already using carboplatin-pemetrexed-bevacizumab for patients with advanced non-squamous NSCLC, but this study suggests there is indeed an improvement in overall survival when bevacizumab is added. What’s more, I was surprised to learn that the survival benefit of bevacizumab persisted even in older patients and after adjusting for brain metastases, hemoptysis, and anticoagulation use,” Bagley added.

The retrospective study used nationally representative electronic health record (EHR) data from Flatiron Health and supplemented these data with the researchers’ institutional experience to account for confounding clinical variables not captured in the Flatiron database.

These data cover a total of 4,724 lung cancer patients treated between January 1, 2011 and June 30, 2017 across more than 260 community cancer clinics. 2,759 patients (58%) received carboplatin/pemetrexed while 1,965 (42%) received carboplatin/pemetrexed/bevacizumab.

The median overall survival improved to 12.1 months in the bevacizumab group versus 8.6 months without; even after adjusting for prognostic variables. In a second cohort including patients from Abramson Cancer Center, an academic institution, the overall survival benefit gain was even greater when bevacizumab was added.

“Despite a lack of randomized clinical trial data, carboplatin and pemetrexed in combination with bevacizumab is a regimen that is used for treating naïve patients with advanced non-squamous NSCLC. Now, with the approval of immunotherapy-containing regimens, this therapeutic approach is reserved for those who are not candidates for immunotherapy,” commented Ticiana Leal, MD, Assistant Professor of Medicine, University of Wisconsin Carbone Cancer Center.

Leal is an associate editor for JNCCN and a member of the NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines®) Panel for Non-Small Cell Lung Cancer.

“In the NCCN Guidelines®, this regimen is included as a category 2A recommendation. While the study is limited by its retrospective and non-randomized nature, potential co-founders, and lack of analysis for cost and toxicity burden, the analysis does provide additional support for the incorporation of bevacizumab in the treatment of advanced NSCLC for selected patients.”

Reference

Bagley SJ, Talento S, Mitra N, Meropol NJ, Cohen RB, Langer CJ, Vachani A. Comparative Effectiveness of Carboplatin/Pemetrexed With Versus Without Bevacizumab for Advanced Nonsquamous Non-Small Cell Lung Cancer. J Natl Compr Canc Netw. 2019 May 1;17(5):469-477. doi: 10.6004/jnccn.2018.7102.