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Nivolumab was the first immune checkpoint inhibitor approved for use in advanced non-small cell lung cancer (NSCLC). This noninterventional, prospective cohort study investigates real-world effectiveness of nivolumab in pretreated NSCLC patients in Germany (Enlarge-Lung/CA209-580). Patients with squamous (SQ) or nonsquamous (NSQ) NSCLC previously treated for locally advanced or metastatic (stage IIIB/IV) disease received nivolumab according to the current Summary of Product Characteristics. Overall survival (OS) was the primary endpoint. Of 907 patients enrolled, 660 patients who were followed for at least 12 months across 79 study centers in Germany, were analyzed. Median OS was 11.2 months [95% confidence interval (CI), 9.1-12.9]; outcomes for the 418 patients with NSQ histology [13.1 mo (95% CI, 10.6-15.6)] were more favorable than outcomes for the 242 patients with SQ histology [8.9 mo (95% CI, 6.4-11.3)]. Patients' age, presence of distant or brain metastases, or line of therapy did not affect outcomes; however, patients with poor performance status (ECOG-PS ≥2, n=80) had shorter median OS [4.7 mo (95% CI, 3.1-5.4)]. This study represents one of the largest real-world cohorts providing outcomes of nivolumab in pretreated NSCLC. The results match well with the published evidence from pivotal clinical trials and demonstrate clinical effectiveness of nivolumab in advanced NSCLC.

BACKGROUND Docetaxel is a widely used cytotoxic agent. This study evaluates the impact of docetaxel toxicities on patient's health-related quality of life (QoL). PATIENTS AND METHODS We conducted a multicenter, prospective, non-interventional trial, in which the QoL was assessed using the EORTC QLQ-C30 questionnaires at baseline and every 4 weeks up to 40 weeks in patients receiving a docetaxel-based chemotherapy for metastatic disease. Treatment-related adverse events were correlated with the corresponding QoL scores. Uni- and multivariate analyses were applied. RESULTS From January 2008 to June 2011, a total of 2659 patients were included. The majority of patients (48.1%) had prostate cancer, followed by breast (17.1%) and non-small-cell-lung cancer (15.8%). Patients received a median of 5 docetaxel cycles with the median dose of 75 mg/m(2). The presence of grade 3/4 diarrhea showed the strongest effect on global health status/QoL average scores (50.91 versus 33.06), followed by vomiting (50.91 versus 35.17), dyspnea (50.94 versus 35.81), mucositis/stomatitis (50.88 versus 36.41), nausea (50.91 versus 36.68), infection (50.90 versus 37.14), fatigue (50.90 versus 43.82) and anemia (50.91 versus 41.03), P < 0.05 for all comparisons. Grade 3/4 leukopenia/neutropenia, alopecia, constipation, neurotoxicity and nail disorders had no significant impact on the global health status/QoL or other items. CONCLUSION In this large non-interventional trial, docetaxel-associated grade 3 or 4 toxicities were shown to have a strong detrimental effect on patient's QoL. Notably, diarrhea and vomiting had the strongest negative impact on QoL measures. This has to be kept in mind while making therapeutic decisions and providing optimized supportive treatment measures. CLINICAL TRIALS NUMBER This study was registered at Deutsches Krebsstudienregister (DKSR, primary registry in the WHO Registry Network) with the ID 527.

This study aimed to prove the usefulness of the diagnostic plot, using the haemoglobin content of reticulocytes as a measure of functional iron deficiency (FID) and the ferritin index as a measure of iron availability, to customise anaemia treatment in cancer patients. Based on results of this plot, cancer patients fulfilling practice guideline criteria to receive erythropoiesis-stimulating agents (ESAs) were allocated to treatment with ESAs alone, iron alone or the combination of both. Primary endpoint was the percentage of patients identified to require iron in addition or as an alternative to ESA therapy. Out of 303 patients screened, 286 were allocated to treatment: 204 patients were normochromic and iron replete and treated with ESAs alone, 22 had both FID and anaemia of chronic disease and were treated with ESAs and parenteral iron, and 60 were iron-depleted and treated with iron only. After 8 weeks, a haemoglobin increase >1 g/dL from baseline was shown by 56% of patients treated with ESAs alone, by 100% of patients receiving the combination, by 50% of normochromic and by 73% of hypochromic iron-depleted patients receiving iron only. Acute phase reaction did not diminish the response rate to ESAs. The diagnostic plot was superior to transferrin saturation and ferritin in predicting iron availability in hypochromic patients treated with ESAs and proved useful to select treatment for anaemia in cancer patients.

9621 Background: Docetaxel is a widely used cytotoxic agent. It causes a number of side effects, most frequently leukopenia and neutropenia, alopecia, nausea, diarrhea, and fatigue. This study eval...

Introduction: In most cancer patients anemia will be attributable to the mechanisms of chronic disease compounded by the myelotoxic effect of chemotherapy. Nevertheless it is important to exclude alternative explanations such as iron deficiency before starting therapy with erythropoiesis stimulating agents (ESA). Recently Thomas et al. (Clin Chem2002;48:1066-76) combined the reticulocyte hemoglobin (Hb) content (CHr) with the C-reactive protein (CRP)-dependent ferritin (Fer) index (FI: soluble transferrin receptor/ log Fer ratio) in a diagnostic plot (DP). We conducted a prospective phase II trial to analyze the diagnostic value of CHr, FI and the DP in anemic chemotherapy treated cancer patients (pts). Methods: Informed consenting pts with an indication for ESA therapy as per EORTC guidelines and a ferritin level ≥20ng/ml were screened with the DP in a central laboratory. DP classifies pts in 1 of 4 quadrants (Q1 – Q4). Those with FI values above threshold (FI ≥3.2 if CRP < 5mg/l, or FI > 2.0 if CRP ≥5 mg/l) were assigned to Q2 (CHr > 28 pg) or Q3 (CHr ≤ 28 pg), and those with sub threshold FI values to Q1 (CHr > 28 pg) or Q4 (CHr ≤ 28 pg). Pts in Q1 received Epoetin beta (Epo) 30.000E/wk sc., those in Q4 additionally Fe-saccharat 200mg/wk iv up to 1g. Pts in Q2 + 3 were treated with oral or iv iron only. Results: 11 centers recruited 303 pts (median age 65 y, male 41%) from 10/04 to 10/06; 230 (76%) had a sub threshold FI (Q1+4), of whom 23 (8%) had a CHr ≤28pg (Q4). 63 pts (21%) fell in Q2+3 with an increased FI, indicating relative iron deficiency, of whom 27 (9%) had a CHr ≤28pg (Q3). There was no correlation between assignment to Q1−4 and age, gender, body-mass-index, type or stage of tumor, measurable metastasis, bonemarrow infiltration, performance status, endogenous epo level, and haematocrit. However, Hb was lower and CRP was higher in Q4. RBC were higher in Q2+3, as leucocytes and thrombocytes were in Q3+4 and transferrin saturation in Q1. In 265 pts. evaluable for response Hb on d1 was 9.8 ± 1.2 g/dl (mean ± SD) and 10.7 ± 1.3 g/dl in 4th week. Mean increase of Hb from d1 to 8th week was 1.4 ± 1.7 g/dl. 36% pts. received a transfusion within 12 weeks and 18% after the 4th week. The table shows response according to Q1−4. Conclusions: Overall response rate was comparable to other ESA studies. However pre therapeutic analysis of hypochromic reticulocytes and ferritin index in the diagnostic plot identifies about a quarter of pts, which were classified in Q2/3 due to elevated FI and had a good response receiving iron only. 8% pts with hypochromic reticulocytes and a sub threshold FI (Q4) had the best Hb-response with epo + iv iron. Table: Response to treatment per quadrant in the diagnostic plot N 265 FI < threshold * FI ≥ threshold * * FI ≥2.0 if CRP 3.2 if CRP ≥5 mg/l CHr >28 pg therapy Hb g/dl mean ± SD d1 4thweek Δ Hb 8th wk-d1 mean ± SD median g/dl (Quartile) % pts. with transfusions within 12 weeks after 4th week Q1 N 194 (73%) Epo only9.9 ± 1 10.7 ± 1.3 1.3 ± 1.5 1.1 (0.3–2.1) 41% 22% Q2 N 31 (12%) Iron only9.6 ± 2 10.4 ± 1.3 1.6 ± 2.4 1.5 (−0.1–2.4) 19% 3% CHr ≤ 28 pg therapy Hb g/dl mean ± SD d1 4thweek ΔHb 8th wk-d1mean ± SD median g/dl (Quartile) % pts. with transfusions within 12 weeks after 4th week Q4 N 21 (8%) Epo + iv iron9.2 ± 1 10.6 ± 1.4 2.3 ± 2 2.2 (0.3–4.1) 33% 19% Q3 N 19 (7%) Iron only 9.2 ± 1.1 10.9 ± 1.1 1.5 ± 1.5 2 (0.1–2.6) 16% 5%