Selumetinib Plus Adjuvant Radioactive Iodine in Patients With High-Risk Differentiated Thyroid Cancer: A Phase III, Randomized, Placebo-Controlled Trial (ASTRA).

PURPOSE: Selumetinib can increase radioactive iodine (RAI) avidity in RAI-refractory tumors. We investigated whether selumetinib plus adjuvant RAI improves complete remission (CR) rates in patients with differentiated thyroid cancer (DTC) at high risk of primary treatment failure versus RAI alone. METHODS: ASTRA (ClinicalTrials.gov identifier: NCT01843062) is an international, phase III, randomized, placebo-controlled, double-blind trial. Patients with DTC at high risk of primary treatment failure (primary tumor > 4 cm; gross extrathyroidal extension outside the thyroid gland [T4 disease]; or N1a/N1b disease with ≥ 1 metastatic lymph node(s) ≥ 1 cm or ≥ 5 lymph nodes [any size]) were randomly assigned 2:1 to selumetinib 75 mg orally twice daily or placebo for approximately 5 weeks (no stratification). On treatment days 29-31, recombinant human thyroid-stimulating hormone (0.9 mg)-stimulated RAI (131I; 100 mCi/3.7 GBq) was administered, followed by 5 days of selumetinib/placebo. The primary end point (CR rate 18 months after RAI) was assessed in the intention-to-treat population. RESULTS: Four hundred patients were enrolled (August 27, 2013-March 23, 2016) and 233 randomly assigned (selumetinib, n = 155 [67%]; placebo, n = 78 [33%]). No statistically significant difference in CR rate 18 months after RAI was observed (selumetinib n = 62 [40%]; placebo n = 30 [38%]; odds ratio 1.07 [95% CI, 0.61 to 1.87]; P = .8205). Treatment-related grade ≥ 3 adverse events were reported in 25/154 patients (16%) with selumetinib and none with placebo. The most common adverse event with selumetinib was dermatitis acneiform (n = 11 [7%]). No treatment-related deaths were reported. CONCLUSION: Postoperative pathologic risk stratification identified patients with DTC at high risk of primary treatment failure, although the addition of selumetinib to adjuvant RAI failed to improve the CR rate for these patients. Future strategies should focus on tumor genotype-tailored drug selection and maintaining drug dosing to optimize RAI efficacy.

Patient-reported outcomes from FLAURA: Osimertinib versus erlotinib or gefitinib in patients with EGFR-mutated advanced non-small-cell lung cancer.

BACKGROUND: In the FLAURA trial, osimertinib demonstrated superior progression-free survival and a favorable toxicity profile to erlotinib or gefitinib as initial therapy in patients with EGFR-mutated advanced non-small-cell lung cancer. Patient-reported outcomes from FLAURA are discussed here. METHODS: Patients (N = 556) completed the EORTC QLQ-LC13 weekly for 6 weeks, then every 3 weeks, and the QLQ-C30 every 6 weeks. Prespecified key symptoms were cough, dyspnea, chest pain, appetite loss, and fatigue. Score changes from baseline to randomized treatment discontinuation were assessed using a mixed-effects model. A ≥10-point change was considered clinically relevant. Odds of improvement and time to deterioration were investigated. QLQ-C30 functioning scores were assessed post hoc. RESULTS: Questionnaire completion rates were >70% at most time points. Baseline mean scores were similar in the osimertinib and erlotinib/gefitinib arms. Scores improved in both arms, but none reached clinical relevance at 5% significance level. A statistically significant difference favoring osimertinib for chest pain was not clinically relevant (-6.84 vs -3.88; p = 0.021). Odds of improvement and time to deterioration were similar between treatments. In post hoc analyses, improvements favored osimertinib for emotional functioning (8.79 vs 4.91; p = 0.004) and social functioning (7.66 vs 1.74; p < 0.001). Cognitive functioning remained stable with osimertinib but deteriorated with erlotinib/gefitinib (0.03 vs -3.91; p = 0.005). CONCLUSIONS: Key symptoms improved from baseline in both treatment arms in FLAURA. Key symptom improvements that were both statistically significant and clinically relevant were not observed in favor of either treatment arm. CLINICAL TRIAL REGISTRATION: NCT02296125.