DREAM3R: Durvalumab with chemotherapy as first-line treatment in advanced pleural mesothelioma—A phase 3 randomized trial.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. TPS8586-TPS8586
Author(s):  
Patrick M. Forde ◽  
Anna K. Nowak ◽  
Peey-Sei Kok ◽  
Chris Brown ◽  
Zhuoxin Sun ◽  
...  
Keyword(s):  
Overall Survival ◽  
Tumour Response ◽  
Control Group ◽  
Pleural Mesothelioma ◽  
Line Treatment ◽  
First Line ◽  
Phase 3 ◽  
Platinum Based Chemotherapy ◽  
Doublet Chemotherapy ◽  
First Line Treatment

TPS8586 Background: Standard first line treatment for unresectable malignant pleural mesothelioma (MPM) is platinum-based chemotherapy with pemetrexed. Two recent, single-arm, phase 2 trials (DREAM1 and PrE05052) combining the PD-L1 inhibitor durvalumab and standard first line cisplatin and pemetrexed (CP) exceeded pre-specified criteria for proceeding to phase 3. DREAM3R aims to determine the effectiveness of adding durvalumab to first line CP chemotherapy in advanced MPM. Methods: Treatment-naïve patients with advanced MPM will be randomised (2:1) to EITHER durvalumab 1500 mg every 3 weeks plus doublet chemotherapy (cisplatin 75 mg/m2 and pemetrexed 500 mg/m2) every 3 weeks for 4-6 cycles, followed by durvalumab 1500 mg every 4 weeks until disease progression, unacceptable toxicity or patient withdrawal; OR doublet chemotherapy alone for 4-6 cycles, followed by observation. The target sample size is 480 patients (320 durvalumab, 160 control) recruited over 27 months, with follow up for an additional 24 months. This provides over 85% power if the true hazard ratio for overall survival is 0.70, with 2-sided alpha of 0.05, assuming a median survival of 15 months in the control group. Key inclusion criteria: MPM of any histological subtype; measurable disease as per RECIST 1.1 modified for mesothelioma (mRECIST 1.1) without prior radiotherapy to these sites; ECOG PS 0-1; and, adequate hematologic, renal, and liver function tests. Key exclusion criteria: prior systemic anticancer treatment for MPM; diagnosis based only on cytology or fine needle aspiration biopsy; contraindication to immunotherapy; and conditions requiring immunosuppressives or corticosteroids. Stratification: Age (18-70 years vs. > 70), sex, histology (epithelioid vs. non-epithelioid), and region (USA vs. ANZ). The primary endpoint is overall survival. Secondary endpoints include progression-free survival; objective tumour response (by mRECIST 1.1 and iRECIST); adverse events; health-related quality of life; and healthcare resource use. Tertiary correlative objectives are to explore and validate potential prognostic and/or predictive biomarkers (including features identified in the DREAM and PrE0505 studies, PD-L1 expression, tumour mutation burden, nuanced genomic characteristics, and HLA subtypes) in tissue and serial blood samples. An imaging databank will be assembled for validation of radiological measures of response, and studies of possible radiomic biomarkers in mesothelioma. Clinical trial information: NCT04334759. and ACTRN 12620001199909.

scholarly journals Vascular endothelial growth factor-A is an Immunohistochemical biomarker for the efficacy of bevacizumab-containing chemotherapy for duodenal and jejunal adenocarcinoma

BMC Cancer ◽  
2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Takahiro Amano ◽  
Hideki Iijima ◽  
Shinichiro Shinzaki ◽  
Taku Tashiro ◽  
Shuko Iwatani ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Overall Survival ◽  
Progression Free Survival ◽  
Vascular Endothelial ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
Platinum Based Chemotherapy ◽  
Endothelial Growth Factor ◽  
First Line Treatment

Abstract Background The efficacy and safety of bevacizumab-containing chemotherapy for patients with metastatic duodenal and jejunal adenocarcinoma (mDJA) are unclear. The present study aimed to evaluate the efficacy of bevacizumab and to explore immunohistochemical markers that can predict the efficacy of bevacizumab for patients with mDJA. Methods This multicentre study included patients with histologically confirmed small bowel adenocarcinoma who received palliative chemotherapy from 2008 to 2017 at 15 hospitals. Immunostaining was performed for vascular endothelial growth factor-A (VEGF-A), TP53, Ki67, β-catenin, CD10, MUC2, MUC5AC, MUC6, and mismatch repair proteins. Results A total of 74 patients were enrolled, including 65 patients with mDJA and 9 with metastatic ileal adenocarcinoma. Patients with mDJA who received platinum-based chemotherapy with bevacizumab as first-line treatment tended to have a longer progression-free survival and overall survival than those treated without bevacizumab (P = 0.075 and 0.077, respectively). Multivariate analysis extracted high VEGF-A expression as a factor prolonging progression-free survival (hazard ratio: 0.52, 95% confidence interval: 0.30–0.91). In mDJA patients with high VEGF-A expression, those who received platinum-based chemotherapy with bevacizumab as a first-line treatment had significantly longer progression-free survival and tended to have longer overall survival than those treated without bevacizumab (P = 0.025 and P = 0.056, respectively), whereas no differences were observed in mDJA patients with low VEGF-A expression. Conclusion Immunohistochemical expression of VEGF-A is a potentially useful biomarker for predicting the efficacy of bevacizumab-containing chemotherapy for patients with mDJA.

Re: Updates in the management and future landscape of urothelial carcinoma

2020 ◽  
pp. 107815522098083
Author(s):  
J Sarkis ◽  
J Assaf
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Standard Of Care ◽  
Line Treatment ◽  
Extensive Review ◽  
First Line ◽  
Metastatic Bladder Cancer ◽  
Platinum Based Chemotherapy ◽  
Future Landscape ◽  
First Line Treatment

Immunotherapy is gradually revolutionizing bladder cancer treatment. In this extensive review published by Hanna et al. in your journal, the authors presented recent studies that are trying to challenge the standard platinum-based chemotherapy as first-line treatment of metastatic bladder cancer by chemoimmunotherapy. However, upfront pembrolizumab, atezolizumab and durvalumab association with standard of care chemotherapy did not improve overall survival when compared to chemotherapy alone. We hereby highlight a study that was not included in this review, the INDUCOMAIN trial, by discussing its results and its future implications on immunotherapy for metastatic bladder cancer.

scholarly journals Vascular Endothelial Growth Factor-A is an Immunohistochemical Biomarker for the Efficacy of Bevacizumab-containing Chemotherapy for Duodenal and Jejunal Adenocarcinoma

2021 ◽  
Author(s):  
Takahiro Amano ◽  
Hideki Iijima ◽  
Shinichiro Shinzaki ◽  
Taku Tashiro ◽  
Shuko Iwatani ◽  
...  
Keyword(s):  
Vascular Endothelial Growth Factor ◽  
Overall Survival ◽  
Progression Free Survival ◽  
Vascular Endothelial ◽  
Line Treatment ◽  
First Line ◽  
Free Survival ◽  
Platinum Based Chemotherapy ◽  
Endothelial Growth Factor ◽  
First Line Treatment

Abstract Background: The efficacy and safety of bevacizumab-containing chemotherapy for patients with metastatic duodenal and jejunal adenocarcinoma (mDJA) are unclear. The present study aimed to evaluate the efficacy of bevacizumab and to explore immunohistochemical markers that can predict the efficacy of bevacizumab for patients with mDJA.Methods: This multicentre study included patients with histologically confirmed small bowel adenocarcinoma who received palliative chemotherapy from 2008 to 2017 at 15 hospitals. Immunostaining was performed for vascular endothelial growth factor A (VEGF-A), TP53, Ki67, β-catenin, CD10, MUC2, MUC5AC, MUC6, and mismatch repair proteins.Results: A total of 74 patients were enrolled, including 65 patients with mDJA and 9 with metastatic ileal adenocarcinoma. Patients with mDJA who received platinum-based chemotherapy with bevacizumab as first-line treatment tended to have a longer progression-free survival and overall survival than those treated without bevacizumab (P = 0.075 and 0.077, respectively). Multivariate analysis extracted high VEGF-A expression as a factor prolonging progression-free survival (hazard ratio: 0.52, 95% confidence interval: 0.30-0.91). In mDJA patients with high VEGF-A expression, those who received platinum-based chemotherapy with bevacizumab as a first-line treatment had significantly longer progression-free survival and tended to have longer overall survival than those treated without bevacizumab (P = 0.025 and P = 0.056, respectively), whereas no differences were observed in mDJA patients with low VEGF-A expression. Conclusion: Immunohistochemical expression of VEGF-A is a potentially useful biomarker for predicting the efficacy of bevacizumab-containing chemotherapy for patients with mDJA.

Health economic analysis of doublet chemotherapy with and without bevacizumab for first-line treatment of RAS mutant metastatic colorectal cancer based on real-world data.

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e16048-e16048
Author(s):  
Koen Degeling ◽  
Hui-Li Wong ◽  
Amanda Pereira-Salgado ◽  
Suzanne Kosmider ◽  
Rachel Wong ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Health Economic ◽  
Overall Survival ◽  
Cost Effectiveness ◽  
Line Treatment ◽  
First Line ◽  
Real World Data ◽  
Third Line ◽  
Doublet Chemotherapy ◽  
First Line Treatment

e16048 Background: Bevacizumab remains the dominant biologic treatment option for RAS mutant (RASmt) metastatic colorectal cancer (mCRC). While the health economic impact of bevacizumab in the RASmt subpopulation may deviate from its use in the general mCRC population, this has never been investigated. This study uses the power of real-world data to assess the cost-effectiveness of doublet chemotherapy with compared to without bevacizumab (ChemBev and ChemOnly, respectively) for first-line treatment of RASmt mCRC, while accounting for subsequent treatment in second and third line. Methods: Data from the Treatment of Recurrent and Advanced Colorectal Cancer (TRACC) registry was analyzed to populate a discrete event simulation of three treatment lines, surgery of primary tumor and metastases, hospitalizations following serious adverse events, and best supportive care. Imbalance in baseline patient and disease characteristics was corrected for in all analyses using inverse probability weights. Costs were included from an Australian public payer perspective in Australian dollars (AUD). All health and economic outcomes were discounted at 5% per year. Results: Of the 507 included RASmt mCRC patients that started first-line treatment in the 2010 – 2017 time period, 345 received ChemBev and 162 ChemOnly. The corrected median time on first-line treatment was 7.1 months (95% confidence interval: 6.4 – 8.0) for ChemBev and 4.1 months (3.5 – 5.1) for ChemOnly. Time on second- and third-line treatment was comparable between the groups. Corrected overall survival was 22.6 months (21.7 – 24.0) for ChemBev and 14.3 months (12.1 – 21.7) for ChemOnly. In terms of the health economic impact, mean life years were 1.9 for ChemBev and 1.5 for ChemOnly, and mean costs were AUD 93,025 and AUD 44,929 per patient, respectively. The resulting incremental cost-effectiveness ratio (ICER) of ChemBev compared to ChemOnly was AUD 149,317 per life-year gained (LYG). Conclusions: In contrast to results from clinical trials, overall survival was substantially longer for patients who received bevacizumab, which can possibly be attributed to an imbalance between groups despite correction for known prognostic factors. At an ICER of AUD 149,317 per LYG, the economic burden of upfront treatment with bevacizumab was found to be substantial and consistent with estimates for the general mCRC population. This is mainly caused by the duration of first-line treatment, which was significantly longer for ChemBev.

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