BackgroundNivolumab, a fully human IgG4 programmed death 1 (PD-1) immune-checkpoint–inhibitor antibody, disrupts PD-1–mediated signaling and may restore antitumor immunity. MethodsIn this randomized, open-label, international phase 3 study, we assigned patients with nonsquamous non–small-cell lung cancer (NSCLC) that had progressed during or after platinum-based doublet chemotherapy to receive nivolumab at a dose of 3 mg per kilogram of body weight every 2 weeks or docetaxel at a dose of 75 mg per square meter of body-surface area every 3 weeks. The primary end point was overall survival. ResultsOverall survival was longer with nivolumab than with docetaxel. The median overall survival was 12.2 months (95% confidence interval [CI], 9.7 to 15.0) among 292 patients in the nivolumab group and 9.4 months (95% CI, 8.1 to 10.7) among 290 patients in the docetaxel group (hazard ratio for death, 0.73; 96% CI, 0.59 to 0.89; P=0.002). At 1 year, the overall survival rate was 51% (95% CI, 45 to 56) with nivolumab ve...

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Nivolumab versus Docetaxel in Advanced Nonsquamous Non–Small-Cell Lung Cancer

Metastatic breast cancer (MBC) is considered incurable; therefore, palliative treatment is the only option. The biologic heterogeneity of the disease is reflected in its somewhat unpredictable clinical behavior. The presence of circulating tumor cells (CTCs) in patients with MBC about to start a new line of treatment has been shown to predict progression-free and overall survival. This prognostic value is independent of the line of therapy (eg, first or second line). Moreover, a multivariate analysis has shown the prognostic value of CTCs to be superior to that of site of metastasis, type of therapy, and length of time to recurrence after definitive primary surgery. These data suggest that the presence of CTCs may be used to modify the staging system for advanced disease. Larger studies are needed to confirm these data and evaluate the use of CTC detection in monitoring treatment and furthering our understanding of breast cancer biology when combined with other diagnostic technologies.

https://www.nejm.org/doi/pdf/10.1056/NEJMoa040766

Circulating Tumor Cells, Disease Progression, and Survival in Metastatic Breast Cancer

https://iris.unito.it/bitstream/2318/1677658/1/OP-ANNO180277%20192..237.pdf

Metastatic non-small-cell lung cancer: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up †

Relevance of breast cancer hormone receptors and other factors to the efficacy of adjuvant tamoxifen: patient-level meta-analysis of randomised trials

Breast cancer is the most common cancer in women in the Western world. Because breast cancer is estrogen-dependent, reducing estrogen secretion by oophorectomy, hypophysectomy, or adrenalectomy can cause the cancer to regress. The need for these surgical procedures was reduced by the introduction of tamoxifen, which acts as an antiestrogen by inhibiting the binding of estrogen to estrogen receptors. Tamoxifen was approved by the Food and Drug Administration in 1977 for the treatment of women with advanced breast cancer and several years later for adjuvant treatment of primary breast cancer.1 Pharmacology and Endocrinology Pharmacologic and Pharmacokinetic Properties The compound administered . . .

Tamoxifen in the Treatment of Breast Cancer

Summary Background Erlotinib is registered for treatment of all patients with advanced non-small-cell lung cancer (NSCLC). However, its efficacy for treatment of patients whose tumours are EGFR wild-type—which includes most patients—is still contentious. We assessed the efficacy of erlotinib compared with a standard second-line chemotherapy in such patients. Methods We did this randomised controlled trial in 52 Italian hospitals. We enrolled patients who had metastatic NSCLC, had had platinum-based chemotherapy, and had wild-type EGFR as assessed by direct sequencing. Patients were randomly assigned centrally (1:1) to receive either erlotinib orally 150 mg/day or docetaxel intravenously 75 mg/m 2 every 21 days or 35 mg/m 2 on days 1, 8, and 15, every 28 days. Randomisation was stratified by centre, stage, type of first-line chemotherapy, and performance status. Patients and investigators who gave treatments or assessed outcomes were not masked to treatment allocation, investigators who analysed results were. The primary endpoint was overall survival in the intention-to-treat population. The study is registered at ClinicalTrials.gov, number NCT00637910. Findings We screened 702 patients, of whom we genotyped 540. 222 patients were enrolled (110 assigned to docetaxel vs 112 assigned to erlotinib). Median overall survival was 8·2 months (95% CI 5·8–10·9) with docetaxel versus 5·4 months (4·5–6·8) with erlotinib (adjusted hazard ratio [HR] 0·73, 95% CI 0·53–1·00; p=0·05). Progression-free survival was significantly better with docetaxel than with erlotinib: median progression-free survival was 2·9 months (95% CI 2·4–3·8) with docetaxel versus 2·4 months (2·1–2·6) with erlotinib (adjusted HR 0·71, 95% CI 0·53–0·95; p=0·02). The most common grade 3–4 toxic effects were: low absolute neutrophil count (21 [20%] of 104 in the docetaxel group vs none of 107 in the erlotinib group), skin toxic effects (none vs 15 [14%]), and asthenia (ten [10%] vs six [6%]). Interpretation Our results show that chemotherapy is more effective than erlotinib for second-line treatment for previously treated patients with NSCLC who have wild-type EGFR tumours. Funding Agenzia Italiana del Farmaco.

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Erlotinib versus docetaxel as second-line treatment of patients with advanced non-small-cell lung cancer and wild-type EGFR tumours (TAILOR): a randomised controlled trial

Tamoxifen alone versus adjuvant tamoxifen for operable breast cancer of the elderly: long-term results of the phase III randomized controlled multicenter GRETA trial

Different types of K-Ras mutations could affect drug sensitivity and tumour behaviour in non-small-cell lung cancer

Between November 1, 1983 and June 30, 1987, 510 node-positive, estrogen receptor (ER)-positive breast cancer patients have been randomly allocated to receive either chemotherapy (six intravenous [IV] cyclophosphamide, methotrexate, and fluorouracil [CMF] courses followed by four IV epirubicin courses) or 5 years of tamoxifen treatment or a combination of both therapies. After a median follow-up of 40 months, patients receiving the combined treatment achieved the best results, and those treated with chemotherapy alone achieved the worst, the difference being particularly evident in postmenopausal women. However, while the concurrent use of chemotherapy and tamoxifen did improve the results achieved by chemotherapy alone, particularly in postmenopausal women and in those with four or more involved nodes, it did not significantly improve the results achieved by tamoxifen alone, particularly in patients with higher ER tumor concentrations. Side effects were more numerous and more severe in patients receiving chemotherapy (with or without tamoxifen). Our findings, although still preliminary, confirm that tamoxifen should be the treatment of choice for postmenopausal breast cancer patients with node-positive, ER-positive tumors. In addition, the findings suggest that tamoxifen may represent a safe alternative to chemotherapy (at least to the cytotoxic regimen we used) for younger women, provided they have ER-positive tumors. In patients with ER-positive tumors, the addition of chemotherapy to tamoxifen does not seem to improve significantly the effectiveness of tamoxifen alone.

Chemotherapy versus tamoxifen versus chemotherapy plus tamoxifen in node-positive, estrogen receptor-positive breast cancer patients: results of a multicentric Italian study. Breast Cancer Adjuvant Chemo-Hormone Therapy Cooperative Group.

A. Scanni

Papers

Erlotinib versus docetaxel as second-line treatment of patients with advanced non-small-cell lung cancer and wild-type EGFR tumours (TAILOR): a randomised controlled trial

Tamoxifen alone versus adjuvant tamoxifen for operable breast cancer of the elderly: long-term results of the phase III randomized controlled multicenter GRETA trial

Different types of K-Ras mutations could affect drug sensitivity and tumour behaviour in non-small-cell lung cancer

Chemotherapy versus tamoxifen versus chemotherapy plus tamoxifen in node-positive, estrogen receptor-positive breast cancer patients: results of a multicentric Italian study. Breast Cancer Adjuvant Chemo-Hormone Therapy Cooperative Group.

Response of thymoma to cetuximab.