Indirect treatment comparison of lurbinectedin versus other second-line treatments for small-cell lung cancer

Aim: Compare lurbinectedin versus other second-line (2L) small-cell lung cancer (SCLC) treatments. Methods: An unanchored matching-adjusted indirect comparison connected the platinum-sensitive SCLC cohort of a single-arm lurbinectedin trial to a network of three randomized controlled trials (oral and intravenous [IV] topotecan, and platinum re-challenge) identified by systematic literature review. Network meta-analysis methods estimated relative treatment effects. Results: In platinum-sensitive patients, lurbinectedin demonstrated a survival benefit and favorable safety profile versus oral and IV topotecan and platinum re-challenge (overall survival, hazard ratio [HR]: 0.43; 95% credible interval [CrI]: 0.27, 0.67; HR: 0.43; 95% CrI: 0.26, 0.70; HR: 0.42; 95% CrI: 0.30, 0.58 respectively). Conclusion: Lurbinectedin showed a robust survival benefit and favorable safety versus other SCLC treatments in 2L platinum-sensitive SCLC

Kaplan Meier survival curve showing patient survival for the presence or absence of HLA-C2 allele in the recipient.

<p>The presence of an HLA-C2 allele in the recipient was associated with a significant improvement in patient survival (10-year survival: 88.5% versus 80.4%).</p

Comparisons are made for ΔMFI of CD86, HLA-DR and CCR7 expression between DCs with either HLA-C1 or HLA-C2 homozygous allele.

<p>Data shown are ΔMFI of CD86, HLA-DR and CCR7 expressed by DC in NK-DC co-culture in the presence of 1 ng/ml IL-15 at cell ratios of either 1∶1 or 1∶5. ΔMFI are calculated as the difference of MFI for DC in co-culture versus DC in isolation i.e. spontaneous expression. In NK-DC co-culture, in the presence of IL-15, DC with HLA-C1 homozygous allele express more co-stimulation molecules, and MHC class II molecules than DC with HLA-C2 homozygous alleles. Furthermore expression of trafficking chemokine CCR7 is virtually exclusive to HLA-C1 homozygotes indicating their predominant role in T-cell immune priming in secondary lymphoid tissues. Data shown for 4 independent experiments performed in each group and * indicates statistical significance with p<0.05 by Mann Whitney U test.</p

Supplementary materials: Indirect treatment comparison of lurbinectedin versus other second-line treatments for small-cell lung cancer

These are peer-reviewed supplementary materials for the article 'Indirect treatment comparison of lurbinectedin versus other second-line treatments for small-cell lung cancer' published in the Journal of Comparative Effectiveness Research.Table S1: Eligibility criteria for screeningTable S2: Search strategy for EmbaseTable S3: Search strategy for MEDLINETable S4: Search strategy for Cochrane Register of Controlled TrialsTable S5: Summary of absolute standardized difference and effective sample size when matched to the basket trial platinum-sensitive subgroup (n = 60)Table S6: Estimated odds ratios and hazard ratios for overall survival and overall response rate across sensitivity analysesTable S7: Estimated odds ratios from the fixed-effect network meta-analysis of hematological adverse eventsFigure S1: Network of trials included in the feasibility assessment, with visualization of platinum sensitivity statusFigure S2: Evidence networks for overall response rate, overall survival, grade 3/4 anemia, grade 3/4 thrombocytopenia, and grade 3/4 neutropenia for (A) sensitivity analysis #1 and (B) sensitivity analysis #2Figure S3: Results from network meta-analysis of progression-free survival/time to progression. Aim: Compare lurbinectedin versus other second-line (2L) small-cell lung cancer (SCLC) treatments. Methods: An unanchored matching-adjusted indirect comparison connected the platinum-sensitive SCLC cohort of a single-arm lurbinectedin trial to a network of three randomized controlled trials (oral and intravenous [IV] topotecan, and platinum re-challenge) identified by systematic literature review. Network meta-analysis methods estimated relative treatment effects. Results: In platinum-sensitive patients, lurbinectedin demonstrated a survival benefit and favorable safety profile versus oral and IV topotecan and platinum re-challenge (overall survival, hazard ratio [HR]: 0.43; 95% credible interval [CrI]: 0.27, 0.67; HR: 0.43; 95% CrI: 0.26, 0.70; HR: 0.42; 95% CrI: 0.30, 0.58 respectively). Conclusion: Lurbinectedin showed a robust survival benefit and favorable safety versus other SCLC treatments in 2L platinum-sensitive SCLC.</p

Cox regression multivariable analysis for all factors that may influence outcomes after kidney transplantation.

<p>Statistically significant associations are indicated in bold.</p

Immunohistochemistry slide demonstrating donor derived CD56 positive cells (anti-CD56 antibody staining brown in colour: arrow as indicator) in pre-transplant kidney biopsy tissue.

<p>In brief, the method for development of this slide included dewaxing and antigen retrieval obtained by W-cap system (Bio-Optica) and staining with mouse monoclonal anti-CD56 antibody (IgG2b Novocastra) used at a dilution of 1∶50 and visualised with the EnVision detection system (DAKO). This image is representative of the observation made for biopsies taken from five different kidney transplants studied. Cell counts (degree of infiltration) were performed using light microscopy and counting 10 randomly selected high power fields at a magnification of 400× (area = 0.17 mm²). Mean (±SEM) of 3±2 CD56 positive cells were identified per high power field.</p

Kaplan Meier survival curve showing death non-censored graft survival for the presence or absence of HLA-C2 allele in the recipient.

<p>The presence of an HLA-C2 allele in the recipient was associated with a significant improvement in death non-censored graft survival (10-year survival: 65.7% versus 43.8%).</p

Causes of graft loss following kidney transplantation.

<p>Causes of graft loss following kidney transplantation.</p

Causes of patient death following kidney transplantation.

<p>Causes of patient death following kidney transplantation.</p