SELECT-2: a phase II, double-blind, randomized, placebo-controlled study to assess the efficacy of selumetinib plus docetaxel as a second-line treatment of patients with advanced or metastatic non-small-cell lung cancer.

BACKGROUND: Combination of selumetinib plus docetaxel provided clinical benefit in a previous phase II trial for patients with KRAS-mutant advanced non-small-cell lung cancer (NSCLC). The phase II SELECT-2 trial investigated safety and efficacy of selumetinib plus docetaxel for patients with advanced or metastatic NSCLC. PATIENTS AND METHODS: Patients who had disease progression after first-line anti-cancer therapy were randomized (2 : 2 : 1) to selumetinib 75 mg b.i.d. plus docetaxel 60 or 75 mg/m2 (SEL + DOC 60; SEL + DOC 75), or placebo plus docetaxel 75 mg/m2 (PBO + DOC 75). Patients were initially enrolled independently of KRAS mutation status, but the protocol was amended to include only patients with centrally confirmed KRAS wild-type NSCLC. Primary end point was progression-free survival (PFS; RECIST 1.1); statistical analyses compared each selumetinib group with PBO + DOC 75 for KRAS wild-type and overall (KRAS mutant or wild-type) populations. RESULTS: A total of 212 patients were randomized; 69% were KRAS wild-type. There were no statistically significant improvements in PFS or overall survival for overall or KRAS wild-type populations in either selumetinib group compared with PBO + DOC 75. Overall population median PFS for SEL + DOC 60, SEL + DOC 75 compared with PBO + DOC 75 was 3.0, 4.2, and 4.3 months, HRs: 1.12 (90% CI: 0.8, 1.61) and 0.92 (90% CI: 0.65, 1.31), respectively. In the overall population, a higher objective response rate (ORR; investigator assessed) was observed for SEL + DOC 75 (33%) compared with PBO + DOC 75 (14%); odds ratio: 3.26 (90% CI: 1.47, 7.95). Overall the tolerability profile of SEL + DOC was consistent with historical data, without new or unexpected safety concerns identified. CONCLUSION: The primary end point (PFS) was not met. The higher ORR with SEL + DOC 75 did not translate into prolonged PFS for the overall or KRAS wild-type patient populations. No clinical benefit was observed with SEL + DOC in KRAS wild-type patients compared with docetaxel alone. No unexpected safety concerns were reported. TRIAL IDENTIFIER: Clinicaltrials.gov NCT01750281.

First-line gefitinib in Caucasian EGFR mutation-positive NSCLC patients: a phase-IV, open-label, single-arm study.

BACKGROUND: Phase-IV, open-label, single-arm study (NCT01203917) to assess efficacy and safety/tolerability of first-line gefitinib in Caucasian patients with stage IIIA/B/IV, epidermal growth factor receptor (EGFR) mutation-positive non-small-cell lung cancer (NSCLC). TREATMENT: gefitinib 250 mg day(-1) until progression. Primary endpoint: objective response rate (ORR). Secondary endpoints: disease control rate (DCR), progression-free survival (PFS), overall survival (OS) and safety/tolerability. Pre-planned exploratory objective: EGFR mutation analysis in matched tumour and plasma samples. RESULTS: Of 1060 screened patients with NSCLC (859 known mutation status; 118 positive, mutation frequency 14%), 106 with EGFR sensitising mutations were enrolled (female 70.8%; adenocarcinoma 97.2%; never-smoker 64.2%). At data cutoff: ORR 69.8% (95% confidence interval (CI) 60.5-77.7), DCR 90.6% (95% CI 83.5-94.8), median PFS 9.7 months (95% CI 8.5-11.0), median OS 19.2 months (95% CI 17.0-NC; 27% maturity). Most common adverse events (AEs; any grade): rash (44.9%), diarrhoea (30.8%); CTC (Common Toxicity Criteria) grade 3/4 AEs: 15%; SAEs: 19%. Baseline plasma 1 samples were available in 803 patients (784 known mutation status; 82 positive; mutation frequency 10%). Plasma 1 EGFR mutation test sensitivity: 65.7% (95% CI 55.8-74.7). CONCLUSION: First-line gefitinib was effective and well tolerated in Caucasian patients with EGFR mutation-positive NSCLC. Plasma samples could be considered for mutation analysis if tumour tissue is unavailable.

Fatal pulmonary fibrosis induced by paclitaxel: a case report and review of the literature.

Fatal lung fibrosis caused by paclitaxel toxicity has not been reported In this report, we describe the case of a 62-year-old woman who received six cycles of paclitaxel and carboplatin as combination chemotherapy for advanced ovarian cancer. Four weeks after the end of the chemotherapy she developed interstitial pneumonitis and irreversible lung fibrosis. Despite treatment with corticosteroids, she had rapid deterioration and died of respiratory failure. Pulmonary fibrosis is a complication of paclitaxel therapy that may occur despite treatments with corticosteroids. While reviewing the literature, we found few less severe pulmonary injuries after intravenous use of paclitaxel, but none of these cases had a fatal outcome. Physicians should keep in mind that taxanes such as paclitaxel have the potential to cause pneumonitis and lung fibrosis.

[Reflections on screening tests for lung cancer]. / Gondolatok a tüdörák szürövizsgálatáról.

Screening for lung cancer is a controversial issue. Much needs to be done in the area of primary prevention of lung cancer. Predictions of lung cancer mortality in Europe indicate further increases in the coming 20 years, due to the extensive number of individuals having long periods of exposure to carcinogens. The treatment of lung cancer is not solved, either, and the global epidemiological situation of lung cancer raises great concerns. Due to these reasons, it seems to be necessary to revise the issue of lung cancer screening. In Hungary, annual minimal mass roentgen screening has been done for decades. The data of more than 4.3 million individuals were analysed in 1996. Out of the symptomless patients detected, 21.4% fell into oncological stage 1, 33.7% into stage 2 and 29% into stage 3. Those patients who were not screened, but who presented with symptoms and were detected as such, can be classified into stages as follows: Stage 1: 8.7%, stage 2: 21.5% and stage 3: 36.3%. The resection rate in the screened group versus non-screened group was 34.3% and 13.7% respectively. Minimal mass roentgen screening allows the detection of lung cancer patients in an earlier stage; with improved treatment possibilities, survival rates and patients' quality of life will shift to a positive direction. It is suggested that the effectiveness of minimal mass roentgen screening of lung cancer should be revised.