RESUMEN
Cancer mostly affects older adults. Despite the increased incidence of cancer among older adults, they are underrepresented in oncology clinical trials. Such trials can provide patients with early access to promising interventions. Clinical trials are changing the future of cancer treatments. This article provides advanced practitioners in oncology an understanding of potential barriers to enrollment of older adults in oncology clinical trials. This article also summarizes the literature comparing tolerance, toxicity, and clinical benefit in the elderly compared with the nonelderly. Enrollment of elderly patients is essential. It is therefore important to create strategies to increase their enrollment. Advanced practitioners, along with other members of the health-care team, play an important role to advocate for elderly patients in phase I clinical trials.
RESUMEN
BACKGROUND: Molecular analysis has revealed four subtypes of pancreatic ductal adenocarcinoma (PDAC). One subtype identified for the presence of DNA damage repair deficiency can be targeted therapeutically with the poly (ADP-ribose) polymerase (PARP) inhibitor olaparib. We performed a single institution retrospective analysis of treatment response in patients with PDAC treated with olaparib who have DNA damage repair deficiency mutations. SUBJECTS, MATERIALS, AND METHODS: Patients with germline or somatic mutations involving the DNA repair pathway were identified and treated with olaparib. The primary objective was to examine the objective response rate (ORR). The secondary objectives were assessing tolerability, overall survival, and change in cancer antigen 19-9. Quantitative texture analysis (QTA) was evaluated from CT scans to explore imaging biomarkers. RESULTS: Thirteen individuals with metastatic PDAC were treated with Olaparib. The ORR to Olaparib was 23%. Median overall survival (OS) was 16.47 months. Four of seven patients with BRCA mutations had an effect on RAD51 binding, with a median OS of 24.60 months. Exploratory analysis of index lesions using QTA revealed correlations between lesion texture and OS (hepatic lesion tumor texture correlation coefficient [CC], 0.683, p = .042) and time on olaparib (primary pancreatic lesion tumor texture CC, 0.778, p = .023). CONCLUSION: In individuals with metastatic PDAC who have mutations involved in DNA repair, Olaparib may provide clinical benefit. BRCA mutations affecting RAD51 binding domains translated to improved median OS. QTA of individual tumors may allow for additional information that predicts outcomes to treatment with PARP inhibitors. IMPLICATIONS FOR PRACTICE: Pursuing germline and somatic DNA sequencing in individuals with pancreatic ductal adenocarcinoma may yield abnormalities in DNA repair pathways. These individuals may receive benefit with poly (ADP-ribose) polymerase (PARP) inhibition. Radiomics and deep sequencing analysis may yet uncover additional information that may predict outcome to treatment with PARP inhibitors.