Introduction: CheckMate 153 (NCT02066636) is a phase 3B/4 study assessing nivolumab in previously treated patients with advanced NSCLC. Eligibility criteria allowed enrollment of patients with poor prognostic features of advanced age or diminished Eastern Cooperative Oncology Group performance status (ECOG PS), which are typically underrepresented in or excluded from randomized controlled trials. Methods: Patients with stage IIIB or IV NSCLC and an ECOG PS of 0 to 2 with disease progression after at least one systemic therapy received nivolumab (3 mg/kg every 2 weeks) until progression, unacceptable toxicity, or consent withdrawal. The primary end point was the incidence of grade 3 to 5 select treatment-related adverse events (TRAEs). Results: Among 1426 treated patients, 556 (39%) were aged 70 years or older and 128 (9%) had an ECOG PS of 2. The median treatment duration was 3.2 months. Across subgroups and the overall population, the incidences of select grade 3 to 5 TRAEs (6%-9%) and grade 3 or 4 TRAEs (12%-14%) were similar. One grade 5 TRAE was documented. The median overall survival time was comparable in the overall population (9.1 months) and patients aged 70 years or older (10.3 months) but shorter in patients with an ECOG PS of 2 (4.0 months). Patient-reported outcomes generally improved. Conclusions: Data from this large predominantly community-based study, which included patients aged 70 years or older and with an ECOG PS of 2, are consistent with registrational studies. As expected, the median overall survival for patients with an ECOG PS of 2 was lower than for the overall population but comparable with historical data.

No abstract

Background: Apatinib is a tyrosine kinase inhibitor which selectively inhibits VEGFR-2 and also represents mild inhibition to PDGFR, c-Kit and c-src. It is an orally bioavailable, small molecule agent which is thought to inhibit angiogenesis and tumor cell proliferation. Previous clinical trials have demonstrated its obvious antitumor activity in various cancer type. Thus we designed this phase II, open-label, single-armed, prospective study (NCT02515435) to investigate the efficacy and safety of apatinib for heavily treated, advanced non-squamous NSCLC patients who are not applicable to current standardized therapy or other clinical trials. Methods: We prospectively enrolled 40 patients with previously heavily treated advanced non-squamous NSCLC. All patients received apatinib with a dose of 500mg, q.d., p.o. Efficiency was evaluated initially 4 weeks later and then every 8 weeks until disease progression, death, or unacceptable toxicity. The primary end point of this study was overall response rate (ORR). The secondary end points were progression-free survival (PFS), overall survival (OS). Results: Forty patients were enrolled in the study with a median age of 61. 15% of patients received apatinib as second-line therapy, 40% of patients received apatinib as third-line therapy, and 60% as forth-line to twelfth-line therapy. Nine patients were found with activated EGFR mutation. Among all the enrolled patients, 38 patients had clinical evaluation and the other 2 received treatment of apatinib less than one month. Within 33 patients who had available image efficiency, 6 were identified as PR,17 SD and 10 PD, no CR was observed. The ORR was 18.18 %, the DCR was 69.69%. The ORR for patients with EGFR mutation positive and negative were 25% and 16% separately. The median PFS was 3.22 months (95% CI, 2.20-4.17 months). Among them, 6 patients received the treatment of apatinib more than five months. The 6-month OS rate was 76.98% (95% CI, 61.68%-92.27%), the 12-month OS rate was 57.48% (95% CI, 28.75%-86.20%). Common treatment-related adverse events were proteinuria (25%), hypertension (17.5%), and hand-foot-skin reaction (HFSR)(27.5%). Severe adverse events included grade 3 hypertension (5%), HFSR (5%), and thrombocytopenia (5%), no grade 4 or 5 adverse events were observed. No un-expected adverse events were found. Conclusion: Apatinib as a monotherapy had a promising overall response together with an acceptable side effect in patients with previously heavily treated advanced non-squamous NSCLC. A phase III study comparing apatinib monotherapy with placebo as 3rd/ 4th setting in advanced non-squamous NSCLC is ongoing to further evaluated the efficacy of apatinib (NCT02332512).Background: CheckMate 153 (NCT02066636) is an ongoing, predominantly community-based, phase 3B/4 safety study of nivolumab in patients with previously treated metastatic NSCLC in the US/Canada. Here we report safety, efficacy, and patient-reported outcome (PRO) data for subgroups of patients aged 70 years or with a poor baseline ECOG PS (PS2). M...

A 3 4 7 -A 7 6 6 of the DCEs for QLU-C10D utility elicitation in cancer patients. Methods: We aimed at 40 "think-aloud" cognitive interviews on feasibility and appropriateness in a heterogeneous sample of cancer patients (exclusion criteria: cognitive impairments, age < 18 and > 85, expected survival time < 6 months). Exactly the same survey material and design as in general population valuations were used, i.e. web-based presentation, 16 binary choice sets per respondent, hypothetical health states including 10 quality of life attributes and a survival time (1, 2, 5, 10 years). Number and reasons for non-participation were recorded. Results: 120 patients were approached and 42 interviews could be completed (43% female, mean age 59.3+-13.5 years, diagnoses: thyroid, breast, lung, pancreatic, haematological, and gastrointestinal cancers; stages: UICC 1 to 4; active treatment 64%, chemotherapy 48%, radiation therapy 45%, surgery only: 7%). Reasons for non-participation were largely organisational and required time resources. Most patients appreciated being asked about their perspective on quality of life and survival time and in principle would be willing to do the DCEs web-based. The trading-off was perceived very burdensome by 11% through evoking thoughts about their own death. Other points of criticism raised by more than 10% of patients were: too many choice sets; explanation was insufficient. For 26% of patients no changes were necessary. ConClusions: Apparently web-based DCEs for the valuation of the QLU-C10D are feasible for cancer patients. Survey adaptations to cancer patients' needs need to be discussed carefully against the background of comparability with general population utilities.objeCtives: This study utilized in-trial data to evaluate the validity and reliability of scores of 3 patient reported outcomes (PRO): Gastrointestinal (GI) Symptom Diary, Modified Satisfaction with Iron Chelation Therapy (MSICT) Questionnaire and Palatability Questionnaire. Methods: This was a randomized, open-label, multi-center, 2-arm, phase 2 study to evaluate the safety of Deferasirox film-coated tablet and Deferasirox dispersible tablet formulations in patients with transfusiondependent thalassemia or myelodysplastic syndrome treated for 24 weeks (wks). PROs were administered at wks 2, 3, 13 and end of treatment (EOT). Upon completion of data collection, psychometric analyses were conducted and included reliability (i.e. test-retest, internal consistency using Cronbach's α ), construct-related validity (including convergent and discriminant validity correlation estimates and conducting a set of known-groups analyses), and distribution-based testing. Results: Data were available for 154 patients for the MSICT and Palatability Questionnaires and for 149 patients for GI Symptom Diary (at either wks 2, 3, 13 or EOT). 51% of the patient population was females with a mean age of 35 years. All PRO scores demonstrated adequate test-retest reliability (intra-class correlations ≥ 0.69). Internal consistency reliability estimate...

Objectives: Friedreich ataxia (FRDA) is a rare disorder with progressive neurodegeneration and cardiomyopathy. Luvadaxistat (also known as TAK-831; NBI-1065844), an inhibitor of the enzyme D-amino acid oxidase, has demonstrated beneficial effects in preclinical models relevant to FRDA. This phase 2, randomized, double-blind, placebo-controlled, parallel-arm study evaluated the efficacy and safety of oral luvadaxistat in adults with FRDA. Methods: Adult patients with FRDA were randomized 2:1:2 to placebo, luvadaxistat 75 mg twice daily (BID), or luvadaxistat 300 mg BID for 12 weeks. The primary endpoint changed from baseline at week 12 on the inverse of the time to complete the nine-hole peg test (9-HPT À1 ), a performance-based measure of the function of the upper extremities and manual dexterity. Comparisons between luvadaxistat and placebo were made using a mixed model for repeated measures. Results: Of 67 randomized patients, 63 (94%) completed the study. For the primary endpoint, there was no statistically significant difference in change from baseline on the 9-HPT À1 (seconds À1 ) at week 12 between placebo (0.00029) and luvadaxistat 75 mg BID (À0.00031) or luvadaxistat 300 mg BID (À0.00059); least squares mean differences versus placebo (standard error) were À0.00054 (0.000746) for the 75 mg dose and À0.00069 (0.000616) for the 300 mg dose. Luvadaxistat was safe and well tolerated; the majority of reported adverse events were mild in intensity. Interpretation: Luvadaxistat was safe and well tolerated in this cohort of adults with FRDA; however, it did not demonstrate efficacy as a treatment for this condition.