A review of clinical trials of cetuximab combined with radiotherapy for non-small cell lung cancer

Abstract

Treatment of non-small cell lung cancer (NSCLC) is challenging in many ways. One of the problems is disappointing local control rates in larger volume disease. Moreover, the likelihood of both nodal and distant spread increases with primary tumour (T-) stage. Many patients are elderly and have considerable comorbidity. Therefore, aggressive combined modality treatment might be contraindicated or poorly tolerated. In many cases with larger tumour volume, sufficiently high radiation doses can not be administered because the tolerance of surrounding normal tissues must be respected. Under such circumstances, simultaneous administration of radiosensitizing agents, which increase tumour cell kill, might improve the therapeutic ratio. If such agents have a favourable toxicity profile, even elderly patients might tolerate concomitant treatment. Based on sound preclinical evidence, several relatively small studies have examined radiotherapy (RT) with cetuximab in stage III NSCLC. Three different strategies were pursued: 1) RT plus cetuximab (2 studies), 2) induction chemotherapy followed by RT plus cetuximab (2 studies) and 3) concomitant RT and chemotherapy plus cetuximab (2 studies). Radiation doses were limited to 60-70 Gy. As a result of study design, in particular lack of randomised comparison between cetuximab and no cetuximab, the efficacy results are difficult to interpret. However, strategy 1) and 3) appear more promising than induction chemotherapy followed by RT and cetuximab. Toxicity and adverse events were more common when concomitant chemotherapy was given. Nevertheless, combined treatment appears feasible. The role of consolidation cetuximab after RT is uncertain. A large randomised phase III study of combined RT, chemotherapy and cetuximab has been initiated.

Differential Superiority of Heavy Charged-Particle Irradiation to X-Rays: Studies on Biological Effectiveness and Side Effect Mechanisms in Multicellular Tumor and Normal Tissue Models

“…Recent therapeutic strategies target the epidermal growth factor receptor (EGFR), which is overexpressed in about 40–50% of GBMs ( 15 ). There is evidence in the literature for such anti-EGFR therapeutics to improve the efficacy of conventional radiotherapy ( 16 ). EGFR is a member of the cell-surface receptor family ErbB and functions as an oncogene.…”

Cost-effectiveness of adjuvant paclitaxel and trastuzumab for early-stage node-negative, HER2-positive breast cancer

“…Several studies reported the cost-effectiveness of widely accepted breast cancer therapies and found favorable ICERs [10,15,20]. For instance, anthracycline-based adjuvant trastuzumab regimen for a 49-year-old women with early-stage HER2-positive breast cancer had an ICER of $39,892/QALY [10], adjuvant trastuzumab chemotherapy for women with HER2-positive breast cancer had an ICER of $26,417/QALY [15], and a more recent study by Hedden et al reported that the adjuvant trastuzumab chemotherapy for women with HER2-positive breast cancer has an ICER of $13,095/QALY [20].…”

Cetuximab for treating non-small cell lung cancer

“…Recruitment for the RT intensification hypothesis was terminated earlier due to futility but recruitment for cetuximab met its accrual endpoint and 465 patients wer available for analysis (42 (38). Median OS were 15.1 and 19.6 months respectively, which favorably compares to historical controls of similar populations treated with radiotherapy alone (43). If this approach resists the test of randomized trials, it may have some benefit in this difficult to treat population.…”