A Comparison of White and African American Outcomes from a Three-Arm, Randomized, Phase III Multicenter Trial of Advanced or Metastatic Non-small Cell Lung Cancer

PURPOSE: To investigate the effect of race on the efficacy and safety of standard chemotherapy doublet regimens in African American patients, we conducted a subgroup analysis of a phase III randomized trial. PATIENTS AND METHODS: Chemonaïve patients with a performance status of 0 or 1 and stage IIIB or IV non-small cell lung cancer were randomized to arm A: gemcitabine 1000 mg/m2 on days 1 and 8 plus carboplatin area under the curve 5.5 on day 1; arm B: the same schedule of gemcitabine plus paclitaxel 200 mg/m2 on day 1; or arm C: paclitaxel 225 mg/m2 on day 1 plus carboplatin area under the curve 6.0 on day 1. Cycles were repeated every 21 days up to 6. A site selection tool identified institutions with potential to recruit a minority population. Outcome and toxicity data of white and African American patients were compared. RESULTS: Of 1135 total patients, 972 were white (85.6%) and 138 were African American (12.2%). Median survival was 8.3 months for white patients (95% confidence interval [CI]: 7.7-9.3) and 9.1 months for African American patients (95% CI: 8.2-11.1). Response rates were 29.1 and 29.0%, respectively. Rates of grade 3 or 4 toxicities were comparable. Among African Americans, median survival was 7.2 months (95% CI: 5.1-10.1) for gemcitabine-carboplatin (n = 47), 10.5 months (95% CI: 7.1-15.4) for gemcitabine-paclitaxel (n = 42), and 10.2 months (95% CI: 8.5-13.2) for paclitaxel-carboplatin (n = 49). CONCLUSION: Whites and African Americans had similar outcomes, although there was some variability in survival among African Americans across the three treatment groups

DuRvalumab with chEmotherapy as first line treAtment in advanced pleural Mesothelioma: A phase 3 randomised trial. The DREAM3R trial

Objective: Until recently, standard first-line treatment for advanced mesothelioma was platinum chemotherapy with pemetrexed. Two recent, single-arm, phase 2 trials (DREAM and PrE0505) combining durvalumab with platinum-pemetrexed chemotherapy exceeded pre-specified criteria. DREAM3R aims to determine the effectiveness of adding durvalumab to platinum chemotherapy in advanced mesothelioma. Methods: Treatment naïve patients with advanced mesothelioma will be randomised (2:1) to either (A) durvalumab 1500 mg 3-weekly, with chemotherapy (Cisplatin 75 mg/m2 or Carboplatin AUC5, and pemetrexed 500 mg/m2) 3-weekly for four to six cycles, followed by durvalumab 1500 mg 4-weekly until disease progression, unacceptable toxicity or patient withdrawal; or (B) chemotherapy alone for four to six cycles, followed by observation. Stratification: Age (18-70 years vs. > 70), gender, histology (epithelioid vs. non-epithelioid), platinum drugs (cisplatin vs carboplatin) and region (ANZ vs USA vs others). An amendment is undergoing to add upfront carboplatin AUC 5 as a platinum choice and as a stratification factor. Key inclusion criteria: MPM of all histologies, measurable disease per modified RECIST 1.1 (mRECIST 1.1) without prior radiotherapy to these sites, ECOG 0-1 and adequate bone marrow, kidney and liver function tests. 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 endpoints: Potential prognostic and/or predictive biomarkers: PD-L1 expression, tumour mutation burden and nuanced genomic characteristics, and HLA type in tissue and serial blood samples; validation of radiological measures of response and studies of possible radiomic biomarkers in mesothelioma. The target sample size is 480 patients recruited over 27 months, with follow up for another 24 months. This provides over 85% power if the true hazard ratio for overall survival was 0.70, with two-sided alpha of 0.05, and assuming a median survival of 15 months in the control group. ClinicalTrials.gov Identifier: NCT04334759 and ACTRN 12620001199909.</p