Cetuximab Finds Niche in Non-Small Cell Lung Cancer

“Adding the EGFR inhibitor cetuximab (Erbitux) to chemotherapy failed to improve survival in patients with advanced non-small cell lung cancer, a multicenter randomized trial showed.

“The primary analysis showed a median overall survival of 10.9 months compared with 9.4 months, a difference that did not achieve statistical significance (HR 0.94, 95% CI 0.84-1.06). The trial also failed to demonstrate improvement in progression-free survival for patients with EGFR-positive disease, the co-primary endpoint.

“However, cetuximab led to a 25% reduction in hazard ratio among patients who had EGFR-positive tumors by fluorescence in situ hybridization (FISH) and were not candidates for bevacizumab (Avastin), a prespecified secondary endpoint. An exploratory analysis analysis showed that patients with EGFR-positive, squamous-cell tumors lived almost twice as long with cetuximab as with chemotherapy alone (11.8 vs 6.4 months, P=0.006), as reported here at the World Conference on Lung Cancer.”


Adding Higher Dose Radiation or Cetuximab Doesn't Benefit Stage III NSCLC Patients Receiving Chemoradiation

The gist: An attempt to improve treatment for stage III non-small cell lung cancer (NSCLC) patients failed when it was tested in a clinical trial. People with stage III NSCLC are normally treated with radiation and chemotherapy. Researchers wondered if giving higher-dose radiation or adding the drug cetuximab (Erbitux) would improve the standard treatment. However, when tested in patients, neither approach worked better than the standard approach.

“As reported in The Lancet Oncology by Bradley and colleagues, the phase III Radiation Therapy Oncology Group 0617 trial showed no survival benefit of high- vs standard-dose radiotherapy or for addition of cetuximab (Erbitux) to concurrent paclitaxel-carboplatin chemoradiation in patients with inoperable stage IIIA or IIIB non–small cell lung cancer (NSCLC).

“In the open-label 2×2 factorial trial, patients from the United States and Canada were randomly assigned 1:1:1:1 between November 2007 and November 2011 to receive 60 Gy radiotherapy (n = 166), 74 Gy radiotherapy (n = 121), 60 Gy radiotherapy and cetuximab (n = 147), or 74 Gy radiotherapy and cetuximab (n = 110) with all patients receiving concurrent once-weekly chemotherapy with paclitaxel at 45 mg/m2 and carboplatin at area under the curve (AUC) 2. Two weeks after chemoradiation, patients received two cycles of consolidation paclitaxel at 200 mg/m2 and carboplatin at AUC 6 separated by 3 weeks. Radiation was given in 2-Gy daily fractions with either intensity-modulated or three-dimensional conformal radiation therapy. Cetuximab was given at 400 mg/m2 on day 1 followed by 250 mg/m2 weekly continued through consolidation therapy. The primary endpoint was overall survival.

“Patients had a median age of 64 years, and most were male (55%–64%), white (82%–89%), had Zubrod performance status of 0 (55%–59%), were current smokers (43%–51%), received three-dimensional conformal radiotherapy (47%–54%), underwent positron-emission tomography (PET) staging (89%–91%), had squamous histology (42%–47%), and had stage IIIA disease (63%–66%).”


Higher Bar Set for Trials in Advanced Colorectal Cancer

Editor’s note: This article describes the results of a clinical trial—a research study with volunteer patients. The goal of the trial was to compare four different treatments for metastatic colorectal cancer (mCRC). All patients took a combination of chemotherapy drugs; either FOLFIRI [which combines folinic acid, fluorouracil and irinotecan] or FOLFOX [folinic acid, 5-fluorouracil and oxaliplatin]. Patients also took a targeted drug alongside the chemo; either bevacizumab (aka Avastin) or cetuximab (Erbitux). All four treatment combinations resulted in similar survival times—a median of 29 months. Compared to other clinical trials, this is a relatively long survival time. Based on these results, oncologists will now have more options for treating their patients according to patients’ preferences and side effects.

“Patients with KRAS wild-type metastatic colorectal cancer (mCRC) receiving first-line treatment with a chemotherapy backbone plus bevacizumab or cetuximab survived for a median of 29 months, the longest median survival time reported in a major trial of these severely ill patients.

“Importantly, survival times were the same, whether patients received the anti–vascular endothelial growth factor bevacizumab (Avastin, Genentech) or the anti–epidermal growth factor receptor (EGFR) cetuximab (Erbitux, Bristol-Myers Squibb), or whether they received FOLFOX or FOLFIRI, results from the long-awaited Phase III CALGB/SWOG 80405 trial showed.

“ ‘What this tells us is that either FOLFIRI [folinic acid, fluorouracil and irinotecan] or FOLFOX [folinic acid, 5-fluorouracil and oxaliplatin] with either bevacizumab or cetuximab are perfectly reasonable options,’ said Alan P. Venook, MD, the Madden Family Distinguished Professor of Medical Oncology and Translational Research at the University of California, San Francisco.”


No Difference in Response Rate but Overall Survival Benefit With First-Line FOLFIRI/Cetuximab vs FOLFIRI/Bevacizumab in Metastatic Colorectal Cancer

Editor’s note: Researchers organized a clinical trial with volunteer patients to compare two treatments for people with metastatic colorectal cancer. All patients in the trial took a chemotherapy treatment called FOLFIRI. (FOLFIRI combines the drugs fluorouracil, leucovorin, and irinotecan.) Some of the patients were also given the drug cetuximab, and the rest took the drug bevacizumab along with FOLFIRI. The patients who took FOLFIRI plus cetuximab survived significantly longer than the patients who took FOLFIRI plus bevacizumab.

“In a European phase III FIRE-3 trial reported in The Lancet Oncology, Heinemann et al found no difference in response rate, the primary endpoint, between FOLFIRI (fluorouracil, leucovorin, and irinotecan) plus the anti-EGFR antibody cetuximab (Erbitux) vs FOLFIRI plus the anti-VEGF-A antibody bevacizumab (Avastin) in first-line treatment of patients with metastatic colorectal cancer. The cetuximab-containing regimen was associated with a significant overall survival advantage…

“In this open-label trial, 592 patients with KRAS exon 2 codon 12/13 wild-type metastatic colorectal cancer aged 18 to 75 years from centers in Germany and Austria were randomly assigned between January 2007 and September 2012 to receive FOLFIRI plus either cetuximab (n = 297) or bevacizumab (n = 295). The primary endpoint was objective response in the intention-to-treat population. The study has completed recruitment, but patient follow-up is ongoing.”


Novel Immune-Based Cancer Drug Imprime PGG Appears Effective in Certain Lung Cancer Patients

Adding the drug Imprime PGG to chemotherapy and antibody therapy may be effective for certain patients with non-small cell lung cancer (NSCLC). Imprime PGG contains a molecule called beta glucan, which can stimulate the body’s immune cells to destroy cancer cells. This process may be especially effective in patients with high levels of immune system proteins that bind to beta glucan, so-called antibeta glucan antibodies. In a recent clinical trial, patients with advanced NSCLC received the antibody drug cetuximab (Erbitux) and the chemotherapy agents carboplatin (Paraplatin) and paclitaxel (Taxol/Abraxane), and some were also given Imprime PGG. While survival across all patients was not affected by Imprime PGG treatment, it was increased in Imprime PGG-treated patients with high levels of antibeta glucan antibodies. Seventeen percent of these patients survived 3 years or more, while none of the other patient groups did.


Four-Drug Combination Shown to Be Safe and Effective for NSCLC

A combination of the drugs carboplatin (Paraplatin), paclitaxel (Taxol/Abraxane), cetuximab (Erbitux), and bevacizumab (Avastin) has demonstrated effectiveness against non-small cell lung cancer (NSCLC) in a phase II clinical trial. One hundred two patients with advanced non-squamous NSCLC received the four-drug combo as a first-line treatment. Tumors shrank in 56% of patients and stopped growing in an additional 21%. Patients went an average of 7 months without their cancer progressing; the average survival time was 15 months. Four treatment-related deaths occurred, including two due to hemorrhage (heavy bleeding), which can be a rare but serious effect of Avastin treatment. This side effect profile was within the predefined safety margin. A phase III trial further investigating this drug combination for NSCLC is currently enrolling participants.


Erbitux-Avastin Combination Plus Chemotherapy in Lung Cancer Is Safe and Effective

Combining cetuximab (Erbitux), bevacizumab (Avastin), and traditional chemotherapy in patients with non-small cell lung cancer (NSCLC) appeared to be safe and effective in a phase II clinical trial. Patients with advanced non-squamous NSCLC received Erbitux and Avastin in addition to carboplatin (Paraplatin) and paclitaxel (Taxol/Abraxane) as first-line treatment, followed by maintenance treatment with Erbitux and Avastin. Tumors shrank in 56% of patients and stopped growing in an additional 21%. Serious side effects were relatively rare; the rate was comparable to that of either Erbitux or Avastin alone. Both Erbitux and Avastin have shown efficacy in NSCLC by themselves, but may be more effective when given together. An ongoing phase III clinical trial will further investigate this drug combination.


Safer, Peptide-Based Therapies Studied as Alternative to Monoclonal Antibodies

Monoclonal antibodies and small-molecule inhibitors have been the primary treatment methods for many types of cancer for many years, but new studies may change that. Peptides, proteins made of small chains of 10 to 50 amino acids, are being examined as possible cost-effective, more successful, safer anticancer vaccines. Researchers have identified two regions on the HER1 (also known as the EGFR) protein as possible targets for these peptide-based drugs. These agents could be used in the treatment of lung cancer, breast cancer, colorectal cancer, and head and neck cancers. If successful, the EGFR-targeting peptide vaccines could be combined with immunotherapies for the HER2 and VEGF proteins, possibly reducing the likelihood that the cancer will develop resistance to the treatment, a common pitfall of monoclonal antibody drugs such as cetuximab (Erbitux).


Standard-Dose Radiation Therapy Safer and More Effective Than High-Dose Therapy in Stage III NSCLC

Standard-dose radiation therapy gives better results compared to high-dose radiation in patients with locally advanced stage III non-small cell lung cancer (NSCLC), a recent clinical trial showed. Patients treated with 60 Gy of radiation had longer median survival (28.7 vs 19.5 months) and higher 18-month survival rates (66.9% vs 53.9%) compared to those receiving 74 Gy of radiation. Standard-dose therapy resulted in less cancer spread, lower rates of recurrence, and fewer severe side effects and treatment-related deaths than high-dose radiation. All patients also received chemotherapy with or without cetuximab (Erbitux) in addition to radiation; a future analysis will look at whether Erbitux helped survival.