Objectives: Soft tissue sarcomas (STSs) are cancers originating in connective tissue; in 50% of cases, patients initially present with or develop advanced or metastatic disease. Prognosis is poor with standard-of-care, anthracycline-containing systemic therapy; median overall survival (OS) is approximately 1 year. A recent phase 2 trial investigated olaratumab, a human anti-platelet-derived growth factor receptor alpha monoclonal antibody, in combination with doxorubicin, for treatment of advanced STS (aSTS). Our objective was to assess the clinical efficacy and safety of olaratumab compared with current standard-of-care therapies in aSTS. MethOds: We conducted a systematic literature review of phase 2 and 3 aSTS trials. Network meta-analyses (NMAs) were conducted for endpoints including OS, progression-free survival (PFS), and discontinuation due to adverse events (AEs). For survival outcomes, NMAs were performed on hazard ratios (HRs) and also using fractional polynomial models (FPMs). Results: A total of 54 comparative studies were identified, of which six studied olaratumab or current standard-ofcare therapies and could be linked in a network. The NMAs analyzed the seven regimens within the network: one regimen each for doxorubicin monotherapy (Dox), olaratumab in combination with doxorubicin (OlaDox), and gemcitabine in combination with docetaxel (GemDoc); and four different dose regimens of ifosfamide in combination with doxorubicin (IfoDox). The OlaDox regimen demonstrated improved OS compared with all included regimens; the improvement was statistically significant (P-values < 0.023 for the HR-based NMA) for all regimens except one IfoDox regimen. OlaDox also showed improved PFS compared with all included regimens; based on FPMs the improvement was statistically significant for Dox, one IfoDox regimen, and GemDoc. For safety, OlaDox showed a significantly lower rate of discontinuation due to AEs compared with all regimens except Dox and one IfoDox regimen. cOnclusiOns: OlaDox demonstrated more favorable results than comparators in terms of aSTS survival endpoints and discontinuation due to AEs.Objectives: Two systematic literature reviews were conducted to assess morbidity and mortality endpoints in patients with stage III or IV melanoma in response to treatment with granulocyte-macrophage colony-stimulating factor (GM-CSF) or dacarbazine (DTIC). MethOds: For this purpose, two literature searches were conducted in the bibliographic databases such as MEDLINE, EMBASE and Cochrane Central Register of Controlled Trials. The systematic literature reviews were based on PICO-(Patient, Intervention, Comparator, Outcome) scheme for inclusion and exclusion criteria. Literature in English and German language was included. Endpoints assessed included overall survival (OS), objective response rate (ORR), and durable response rate (DRR). Results: The review is focused on adult patients with malignant melanoma who were treated with either GM-CSF or DTIC. The two searches identified 105 (GM-CSF) / 379 (DTIC) potentially ...
generated to characterize the diversion of the first TSW event occurring over time for each patient; median time and its 95% confidence interval (CI) was calculated with a prespecified significance level of 0.05. Unadjusted proportional hazard models were conducted to estimate the hazard ratio and its 95% CI. Results: TSW was statistically significant favoring LEN for the QLQ-C30 domains of Role Functioning (2.0 versus 1.9 months in the LEN and SOR arms, respectively; p = 0.0098), Pain (2.0 versus 1.8 months, respectively; p = 0.0060), and Diarrhea (4.6 versus 2.7 months, respectively; p < 0.0001). In the QLQ-HCC18 results favored LEN for the domains of Body Image (2.8 versus 1.9 months, respectively; p = 0.0041) and Nutrition (4.1 versus 2.8 months, respectively; p = 0.0060). The p-values were calculated without multiplicity adjustment ConClusions: Patients on SOR experienced a more rapid clinically meaningful deterioration in terms of Role Functioning, Nutrition (perhaps due to an increased severity of diarrhea), Pain (specifically affecting their daily lives) and Body Image.
S15cohorts. Median overall survival was 9.56 months in the CPX-351 arm and 5.95 months in the 7+3 arm (hazard ratio, 0.69 [95% CI, 0.52-0.90]; 1-sided P = 0.003). By 2 years, 84% of patients in the 7+3 arm had died versus 67% in the CPX-351 arm. Thus, on average, for every 6 patients treated with CPX-351, 1 death would be prevented over 2 years compared with 7+3 (1/(0.84 -0.67)). The CPX-351 safety profile was consistent with the known profile of 7+3. ConCluSionS: CPX-351 improved survival versus 7+3, with an associated NNT of 6 to prevent 1 death at 2 years, supporting the treatment benefit of CPX-351 in adults with newly diagnosed, tAML/AML-MRC.
S15cohorts. Median overall survival was 9.56 months in the CPX-351 arm and 5.95 months in the 7+3 arm (hazard ratio, 0.69 [95% CI, 0.52-0.90]; 1-sided P = 0.003). By 2 years, 84% of patients in the 7+3 arm had died versus 67% in the CPX-351 arm. Thus, on average, for every 6 patients treated with CPX-351, 1 death would be prevented over 2 years compared with 7+3 (1/(0.84 -0.67)). The CPX-351 safety profile was consistent with the known profile of 7+3. ConCluSionS: CPX-351 improved survival versus 7+3, with an associated NNT of 6 to prevent 1 death at 2 years, supporting the treatment benefit of CPX-351 in adults with newly diagnosed, tAML/AML-MRC.
A 3 4 7 -A 7 6 6 A379 cost-effectiveness ratios closest to the threshold as the policy-relevant portion, as this contains the most-effective strategies that approach acceptable cost-effectiveness and therefore should be of most interest to policy makers. Examples from the literature also show how the inclusion of insufficient comparator strategies leads to the under estimation of ICERs or to the mis-identification of inefficient strategies as efficient. The selected examples show how this leads to the mis-identification of the policy-relevant portion of the efficient frontier. ConClusions: Analysts should be aware how the choice of which strategies are simulated influences the estimated efficient frontier and, in turn, which strategies are found to be policy relevant. If possible, CEAs should include a sufficiently broad range of screening interventions to ensure that all the relevant comparator strategies for the policy-relevant portion of the efficient frontier are included.
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