Randomized phase II study on gemcitabine with or without ramucirumab as second-line treatment for advanced malignant pleural mesothelioma (MPM): Results of Italian Rames Study.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. 9004-9004
Author(s):  
Maria Pagano ◽  
Giovanni Luca Ceresoli ◽  
Paolo Andrea Zucali ◽  
Giulia Pasello ◽  
Marina Chiara Garassino ◽  
...  
Keyword(s):  
Phase Ii ◽  
Asbestos Exposure ◽  
Rank Test ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Double Blind ◽  
First Line Therapy ◽  
Line Therapy ◽  
Randomized Phase Ii

9004 Background. The RAMES Study (EudraCT Number 2016-001132-36) is a multicenter, double-blind, randomized phase II trial exploring the efficacy and the safety of the addition of ramucirumab to gemcitabine as the second-line treatment in MPM patients (pts) after platinum/pemetrexed regimens. Methods. The pts were assigned (1:1) to receive Gemcitabine 1000 mg/m2 i v on days 1 and 8 every 21 days with Placebo (Arm A) or Ramucirumab 10 mg/kg i v on day 1, of a 21-day cycle (Arm B), until tolerability or progressive disease. Pts was stratified by ECOG/PS (0-1 vs 2), age (≤ 70 vs > 70 yrs), histology (epithelioid vs non-epithelioid) and time to progression (TTP) after first-line therapy. The primary endpoint was overall survival (OS). Assuming a proportion of OS equal to 40% at 1 year in arm A, a 12% absolute improvement in OS at 1 yrs was expected in Arm B (hazard ratio = 0.70).114 events (156 subjects) are required for a one-sided log-rank test with α = 0.15 to have 80% power. Results. From December 2016 to July 2018, 164 pts were randomized, 81 pts in Arm A and 80 Arm B; 3 pts were randomized but not treated. Characteristics of pts were: median age 69 yrs (44-81), males 119 (73.9%), females 42 (26.1%); ECOG/PS0 96 (59.6%) ECOG/PS1-2 65 (40.4%); histotype epithelioid 132 (81.9%), non-epithelioid 29 (18.1%); stage III 98 (60.7%), stage IV 60 (37.3%), 3 (2.0%) missing; asbestos exposure assessed 80 (49.7%). Median of courses was 3.50 in Arm A and 7.50 in Arm B. OS was significantly longer in Arm B with median 13.8 mths (70% CI 12.7-14.4) vs Arm A with 7.5 mths (70% CI 6.9-8.9), HR 0.71 (70% CI 0.59-0.85, p = 0.057). OS at 6 and 12 mths was in Arm A 63.9% and 33.9%, and in Arm B 74.7% and 56.5%, respectively. In Arm B OS was not correlated to TTP at first-line therapy (13.6 mths in TTP ≤6 mths and 13.9 mths in TTP > 6 mths) and histotypes (13.8 months in the epithelioid and 13.0 months in non-epithelioid). No significant differences in thromboembolism G3-4 events were observed in Arm A vs Arm B (p= 0.64). None hypertension G3-4 was reported in Arm A vs 5 pts (6.3%) in Arm B (p= 0.022). No significant differences in G3-4 haematological toxicities between the two arms were reported. Conclusion: In the RAMES Study the addition of Ramucirumab to Gemcitabine significantly improved OS regardless of age of pts, tumor histotype and TTP at the first-line treatment. Gemcitabine plus Ramucirumab can be considered a manageable regimen in second-line treatment of advanced MPM pts. Clinical trial information: NTC03560973.

Randomized phase II cross-over sequential chemotherapy trial of irinotecan/cisplatin (IP) vs. gemcitabine/vinorelbine (GV) in chemo-naïve patients with stage IIIb/IV non-small cell lung cancer (NSCLC)

2006 ◽  
Vol 24 (18_suppl) ◽  
pp. 7134-7134
Author(s):  
J. S. Lee ◽  
D. H. Lee ◽  
J. J. Lee ◽  
J. Y. Han ◽  
S. H. Park ◽  
...  
Keyword(s):  
Phase Ii ◽  
Response Rate ◽  
Stage Iiib ◽  
Second Line ◽  
Toxicity Profile ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Randomized Phase Ii ◽  
Significant Difference

7134 Background: To compare the efficacy and toxicity of IP vs. non-platinum-based GV in the treatment of advanced NSCLC, we conducted a randomized phase II trial with planned cross-over to the other regimen upon disease progression (PD) after the first-line therapy. Methods: Eligibility required stage IIIb/IV NSCLC, no prior chemotherapy, measurable disease, ECOG PS 0–2, adequate organ functions, and informed consent. After stratification by gender, stage (IIIB or IV) and performance status (PS: 0–1 or 2), eligible pts were randomized to receive either IP (I 65 mg/m2 & P30 mg/m2 on D1 & 8 q 3 weeks) first then GV (G 900 mg/m2 &V25 mg/m2 on D1 & 8 q 3 weeks) upon PD (Arm A) or GV first then IP upon PD (Arm B). Results: Between 12/2003 and 06/2005, 146 pts were enrolled in either Arm A (n = 75) or Arm B (n = 71). There was no difference in gender (male: 77.3% vs. 81.7%), age (median: 58 vs. 60 yrs), PS (PS 2: 10.7% vs. 8.5%), histology (adenocarcinoma: 72.0% vs. 76.6%) and stage (IV: 88.0% vs. 87.3%). IP tended to generate more responses than GN (42.0% vs. 29.0% as first-line, 30.2% vs. 14.3% as second-line), but there was no difference in total response rate by the treatment arm (Arm A: 45.6%, B: 43.5%). During the first-line therapy, IP caused more G3+ anemia (20.0% vs. 7.1%, p = 0.048), G2/3 nausea/vomiting (41.4% vs. 12.9%, p < 0.001), G2 alopecia (35.7% vs. 10.0%, p = 0.001) than GN while pneumonitis was noted only with GN (11.4%). Toxicity profile was similar after the second-line therapy. Both arms resulted in excellent survival outcome with no significant difference between the Arm A and B (median: 16.5 mo vs. 15.1 mo, p = 0.595). Conclusions: Platinum-based IP regimen seemed to be more effective in terms of response rate. Given the overall survival data and the mild toxicity profile of GV regimen, however, either treatment sequence seems to be acceptable for the treatment of advanced metastatic NSCLC. (Supported in part by NCC grants 0210140 and 0510140). No significant financial relationships to disclose.

The combination of thalidomide and intermediate-dose dexamethasone is an effective but toxic treatment for patients with primary amyloidosis (AL)

Blood ◽  
2005 ◽  
Vol 105 (7) ◽  
pp. 2949-2951 ◽  
Author(s):  
Giovanni Palladini ◽  
Vittorio Perfetti ◽  
Stefano Perlini ◽  
Laura Obici ◽  
Francesca Lavatelli ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cells ◽  
Primary Amyloidosis ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
First Line Therapy ◽  
Line Therapy ◽  
Symptomatic Bradycardia ◽  
Intermediate Dose

AbstractBased on the efficacy of thalidomide in multiple myeloma and on its synergy with dexamethasone on myeloma plasma cells, we evaluated the combination of thalidomide (100 mg/d, with 100-mg increments every 2 weeks, up to 400 mg) and dexamethasone (20 mg on days 1-4) every 21 days in 31 patients with primary amyloidosis (AL) whose disease was refractory to or had relapsed after first-line therapy. Eleven (35%) patients tolerated the 400 mg/d thalidomide dose. Overall, 15 (48%) patients achieved hematologic response, with 6 (19%) complete remissions and 8 (26%) organ responses. Median time to response was 3.6 months (range, 2.5-8.0 months). Treatment-related toxicity was frequent (65%), and symptomatic bradycardia was a common (26%) adverse reaction. The combination of thalidomide and dexamethasone is rapidly effective and may represent a valuable second-line treatment for AL.

Economic evaluation of crizotinib, alectinib, ceritinib, and brigatininb in anaplastic lymphoma kinase positive (ALK+) non-small cell lung cancer (NSCLC) as second-line treatment.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e21104-e21104
Author(s):  
Nimer S. Alkhatib ◽  
Briana Choi ◽  
Hala Halawah ◽  
Matthias Calamia ◽  
Dexter Gulick ◽  
...  
Keyword(s):  
Cost Effectiveness ◽  
Adverse Events ◽  
Incremental Cost ◽  
Line Treatment ◽  
Second Line ◽  
First Line ◽  
Reference Drug ◽  
First Line Therapy ◽  
Line Therapy ◽  
Life Years

e21104 Background: Crizotinib, alectinib, ceritinib, and brigatinib are approved as second line treatment for ALK+ NSCLC. Crizotinib was the first ALK inhibitor for first line therapy approved by Food and Drug Administration (2011) then ceritinib (2014), alectinib (2015), and brigatinib (2017) were approved as second line drugs. Following more data, these agents were approved as the first line therapy (2017 for ceritinib and alectinib; 2020 for brigatinib). These remain as a treatment option in patients who fail the first line therapy. Cost-effectiveness/utility analyses were conducted to assess clinical efficacy with varying costs of the agents. Methods: A three state Markov model were assumed (progression free, progression and death). Progression free survival (PFS) curves were digitized and fitted with exponential function. US payer perspective, a lifetime horizon, and discount rate of 3% were applied. Drug costs were Redbook wholesale acquisition cost. Other costs included were monitoring, adverse events and disease progression from published data (US$ 2020). Adverse events reported >5% in patients were included. Measured outcomes were PFS life years (PFSLY) and quality adjusted life years (PFSQALY). Crizotinib was the reference drug. Incremental cost-effectiveness and utility ratios (ICER/ICUR) of PFSLY and PFSQALY gained (PFSLYG, PFSQALYG) and lost were estimated. Base case (BCA) and probabilistic sensitivity analyses (PSA) were conducted. Results: Crizotinib was the reference drug for the following outcomes. For alectinib, with the decremental cost of -$14,653 (-$14,712), the incremental PFSLY of 0.16 (0.16) and PFSQALY of 0.05 (0.05) resulted in an ICER / PFSLYG of -$89,337 (-$88,604) and an ICUR / PFSQALYG of -$269,835 (-$266,510). For brigatinib, with the decremental cost of -$14,975 (-$14,954), the incremental PFSLY of 0.01 (0.01) and PFSQALY of ̃0.01 (0.02) yielded an ICER / PFSLYG of -$1,982,962 (-$1,431,631) and an ICUR / PFSQALYG of -$2,140,534 (-$570,538). For ceritinib, with the incremental cost of $7,590 ($7,514), there were decremental PFSLY of -0.01 (-0.01) and PFSQALY of -0.03 (-0.03). Conclusions: As second line treatment, crizotinib, ceritinib, and brigatinib had comparable PFSLYs and PFSQALYs while alectinib had the most PFSLY and PFSQALY and the lowest cost. Therefore, alectinib is the most cost-effective treatment for treating ALK+ NSCLC as the second line therapy.[Table: see text]

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