Treatment of locoregionally advanced head and neck cancer with concomitant high-dose radiotherapy plus cetuximab improves locoregional control and reduces mortality without increasing the common toxic effects associated with radiotherapy to the head and neck. (ClinicalTrials.gov number, NCT00004227.)

Background Lung cancer is the leading cancer cause of mortality worldwide; large-scale trials have failed to improve clinical outcomes of patients with chemorefractory non-small-cell lung cancer (NSCLC). Methods Following an initial equal randomization period, BATTLE adaptively randomized patients with chemorefractory NSCLC to erlotinib, vandetanib, erlotinib plus bexarotene, or sorafenib based on molecular biomarkers of NSCLC pathogenesis in fresh core needle biopsy specimens. The primary end point was disease control rate (DCR) at 8 weeks. Results Of 255 patients randomly assigned to erlotinib (59 patients), vandetanib (54), erlotinib plus bexarotene (37), and sorafenib (105), 244 were eligible for the DCR analysis. Pneumothorax after lung biopsy occurred in 11.5% and treatment-related toxicities grade 3–4 in 6.5% of patients. Overall results were a 46% 8-week DCR, 1.9-month median progression-free survival, 9-month median overall survival, and 35% 1-year survival. Individual markers predicting a significantly superior DCR for a treatment included: epidermal growth factor receptor (EGFR) mutation (P=0.04) for erlotinib; cyclin D1 positivity (P=0.01) or EGFR amplification (P=0.006) for erlotinib plus bexarotene; vascular endothelial growth factor receptor 2 positivity (P=0.05) for vandetanib; and absence of EGFR mutation (P=0.01) or of EGFR high polysomy (P=0.05) for sorafenib. A better 8-week DCR occurred with sorafenib versus all other regimens (64% versus 33%; P<0.001) among EGFR wild-type patients and versus all other regimens (61% versus 32%; P=0.11) among mutant-KRAS patients. The prespecified biomarker groups were less predictive than the individual biomarkers analyzed in this study. Conclusions The first completed biopsy-mandated study in pretreated NSCLC, BATTLE confirmed our pre-specified hypotheses regarding biomarker and targeted treatment interactions, establishing a new paradigm for personalizing therapy for patients with NSCLC. (ClinicalTrials.gov numbers, NCT00409968, NCT00411671, NCT00411632, NCT00410059, NCT00410189.)

Thoracic radiotherapy moderately improves survival in patients with limited small-cell lung cancer who are treated with combination chemotherapy. Identification of the optimal combination of chemotherapy and radiotherapy will require further trials.

Purpose Patients with advanced, incurable thyroid cancer not amenable to surgery or radioactive iodine (131I) therapy have few satisfactory therapeutic options. This multi-institutional study assessed the activity and safety of axitinib, an oral, potent, and selective inhibitor of vascular endothelial growth factor receptors (VEGFR) 1, 2, and 3 in patients with advanced thyroid cancer. Patients and Methods Patients with thyroid cancer of any histology that was resistant or not appropriate for 131I were enrolled onto a single-arm phase II trial to receive axitinib orally (starting dose, 5 mg twice daily). Objective response rate (ORR) by Response Evaluation Criteria in Solid Tumors was the primary end point. Secondary end points included duration of response, progression-free survival (PFS), overall survival, safety, and modulation of soluble (s) VEGFR. Results Sixty patients were enrolled. Partial responses were observed in 18 patients, yielding an ORR of 30% (95% CI, 18.9 to 43.2). Stable disease lasting ≥ 16 weeks was reported in another 23 patients (38%). Objective responses were noted in all histologic subtypes. Median PFS was 18.1 months (95% CI, 12.1 to not estimable). Axitinib was generally well tolerated, with the most common grade ≥ 3 treatment-related adverse event being hypertension (n = 7; 12%). Eight patients (13%) discontinued treatment because of adverse events. Axitinib selectively decreased sVEGFR-2 and sVEGFR-3 plasma concentrations versus sKIT, demonstrating its targeting of VEGFR. Conclusion Axitinib is a selective inhibitor of VEGFR with compelling antitumor activity in all histologic subtypes of advanced thyroid cancer.