Vaccinating the brain
The epidermal growth factor receptor variant III (EGFRvIII) is often expressed on glioblastoma multiforme (GBM) tumour cells (as well as other tumour types) but not normal cells, which — according to Sampson and colleagues — makes EGFRvIII a potential immunotherapy target for patients with GBM. Sampson and colleagues report a phase II clinical trial of intradermal vaccination with an EGFRvIII-specific peptide (CDX-110) simultaneously with standard or continuous temozolomide (TMZ) in 21 patients with newly diagnosed EGFRvIII+ GBM. Co-administration of TMZ with CDX-110 resulted in sustained immune responses to EGFRvIII in all evaluated patients (95% confidence interval (CI): 0.71–1.00) and the median progression-free survival was 16.6 months (95% CI: 9.1–22.7) compared with 15.2 months (95% CI: 13.9–20.5) in patients treated with TMZ alone. Based on these data a phase III randomized clinical trial has been initiated.
Positively platinum
The lung adjuvant cisplatin evaluation (LACE) study pooled data from the five largest trials that have shown significant overall survival benefit from cisplatin chemotherapy in patients with non-small-cell lung cancer (NSCLC). Pignon and colleagues report that chemotherapy conferred a 5-year absolute benefit of 5.4%, indicating that platinum-based chemotherapy significantly improves survival in patients with NSCLC.
In addition, Scagliotti and colleagues reported a phase III randomized study of cisplatin plus gemcitabine (the standard treatment) and pemetrexed plus cisplatin in 1,725 patients with advanced NSCLC. They found that patients treated with cisplatin plus pemetrexed had the same median survival as patients treated with the standard regimen (10.3 months, 95% CI: 0.84–1.05). However, they found that cancer histology correlated to a preferential response to one of the two combinations. Patients with adenocarcinoma or large-cell carcinoma exhibited longer overall survival when treated with cisplatin plus pemetrexed; whereas patients with squamous cell histology showed significantly improved survival with cisplatin plus gemcitabine (10.8 months versus 9.4 months). They also found that the pemetrexed–cisplatin combination was better tolerated, which suggests that pemetrexed–cisplatin treatment might be beneficial to some patients. This study assesses, for the first time, differences in survival as a result of tumour histology and additional studies using this approach could better inform therapeutic strategies.
References
ORIGINAL RESEARCH PAPER
Sampson, J. H. et al. Effect of EGFRvIII-targeted vaccine (CDX-110) on immune response and TTP when given with simultaneous standard and continuous temozolomide in patients with GBM. J. Clin. Oncol. 26, abstract 2011 (2008)
ORIGINAL RESEARCH PAPERS
Scagliotti, G. V. et al. Phase III study comparing cisplatin plus gemcitabine with cisplatin plus pemetrexed in chemotherapy-naïve patients with advanced-stage non-small-cell lung cancer. J. Clin. Oncol. 27 May 2008 (doi: 10.1200/JCO.2007.15.0375)
Pignon, J.-P. et al. Lung adjuvant cisplatin evaluation: a pooled analysis by the LACE collaborative group. J. Clin. Oncol. 27 May 2008 (doi: 10.1200/JCO.2007.13.9030)
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Trial Watch. Nat Rev Cancer 8, 486 (2008). https://doi.org/10.1038/nrc2436
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DOI: https://doi.org/10.1038/nrc2436