|The following article features coverage from the European Society for Medical Oncology 2020 virtual meeting. Click here to read more of Cancer Therapy Advisor‘s conference coverage.|
The addition of durvalumab plus tremelimumab to standard-of-care chemotherapy did not improve survival or overall response rate (ORR) among patients with previously untreated metastatic pancreatic ductal adenocarcinoma (mPDAC), according to results of a phase 2 trial presented at the European Society of Medical Oncology (ESMO) Virtual Congress 2020.
“Further studies to assess biomarkers that may predict immune sensitivity in this setting are underway and we hope to have this data to present at upcoming conferences,” Daniel Renouf, MD, MPH, FRCPC, of the University of British Columbia in Canada, and presenter of the study, said.
After a safety run-in with 11 patients, the phase 2 Canadian Cancer Trials Group PA.7 trial randomly assigned 180 patients with treatment-naive mPDAC in a 2:1 ratio to receive durvalumab plus tremelimumab with gemcitabine and nab-paclitaxel, or gemcitabine plus nab-paclitaxel alone. Of those 180 patients, 174 had baseline blood samples available for evaluation.
The primary endpoint was overall survival (OS) and the secondary endpoints included progression-free survival (PFS), ORR, and safety. Patients had to have Eastern Cooperative Oncology Group (ECOG) performance status scores of 0 and 1 and were ineligible if they had symptomatic or uncontrolled brain metastases.
At baseline, the median patient age was 65 years, 49% were male, and 89% of patients were white. Most patients had an ECOG performance status of 1 and 11% had received prior adjuvant chemotherapy.
Cell-free DNA analysis was conducted and identified 1 case of high microsatellite instability with a tumor mutational burden of 52.9 mut/Mb.
Durvalumab plus tremelimumab did not provide additional benefit over chemotherapy for any of the outcomes. After a median follow-up of 28.5 months, there was no difference in OS, with a median OS of 9.8 months in the durvalumab-tremelimumab arm compared with 8.8 months in the chemotherapy-only arm (hazard ratio [HR], 0.94; 90% CI, 0.71-1.25; P =.72). The lack of OS benefit with immunotherapy was consistent across subgroups.
PFS was also similar between arms, with a median of 5.5 and 5.4 months with durvalumab-tremelimumab or chemotherapy only, respectively (HR, 0.98; 90% CI, 0.75-1.29; P =.91).
The ORR was 30.3% with durvalumab plus tremelimumab compared with 23% with chemotherapy, which was not significant (P =.28). The disease control rate was 70.6% in the durvalumab plus tremelimumab arm compared with 57.4% in the chemotherapy-only arm, which was also not significant (P =.10). There were no complete responses.
The rates of adverse events (AEs) were similar between the arms, except grade 3 or higher lymphopenia occurred more frequently in the durvalumab plus tremelimumab arm compared with the other cohort (38% vs 20%, respectively; P =.02).
Disclosures: The study was funded by AstraZeneca. Some of the presenters reported financial relationships with the pharmaceutical industry. For a full list of disclosures, please refer to the original abstract.
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Renouf DJ, Knox JJ, Davan P, et al. The Canadian Cancer Trials Group PA.7 trial: Results of a randomized phase II study of gemcitabine (GEM) and nabpaclitaxel (Nab-P) vs GEM, nab-P, durvalumab (D) and tremelimumab (T) as first line therapy in metastatic pancreatic ductal adenocarcinoma (mPDAC). Presented at: European Society of Medical Oncology (ESMO) Virtual Congress 2020; September 19-21, 2020. LBA65.