Is Personalization of Care Coming to Pancreatic Oncology?

Abstract

The results of a phase II trial evaluating adjuvant treatment using a novel way of administering gemcitabine with radiation in patients with resected pancreatic cancer are presented in this issue of the Annals of Surgical Oncology. The trial was designed to evaluate local tumor control as the primary endpoint, using historical local tumor control rates of less than 60 % derived from results reported from cooperative group trials and seeking to show a 2-year local tumor control rate of over 80 % with this novel regimen. The authors reported that the local tumor control rate was apparently improved, without impacting overall survival. Thus, although the primary endpoint was met, there was no identifiable improvement in outcome. As the authors have concluded, future trials should focus on improving systemic disease control due to the high rate of distant metastatic disease in these patients. Adjuvant trials should be designed with overall survival as the primary endpoint. The use of local tumor control as a primary endpoint is problematic in pancreatic cancer for several reasons. Local tumor control is necessary but not sufficient to cure a patient of pancreatic cancer due to the competing risk of distant metastatic disease. Even if the local tumor is controlled, most patients will die of distant disease. As distant disease control is improved in the future with the development of novel systemic therapies, the impact of local tumor recurrence on overall survival could be greater. Until that happens, local tumor control will have a modest impact on overall survival even in the most highly selected patients. Another problem is the heterogeneity of patient selection and surgical quality in cooperative group trials as well as the lack of consistency in identifying and reporting local disease recurrence, which makes the historical local tumor control rate difficult to define. Although clearly there have been many studies that have reported high rates of local tumor recurrence after pancreaticoduodenectomy, the use of chemoradiation is controversial. Patients with resected pancreatic cancer should be enrolled on the current Radiation Therapy Oncology Group (RTOG)-led adjuvant trial, RTOG/INT 0848. That trial randomizes patients to receive gemcitabine with or without erlotinib for five cycles followed by a second randomization to chemoradiation or a sixth cycle of chemotherapy. Off-protocol, the preferred standard treatment is initial gemcitabine for 4‐6 cycles followed by consideration of chemoradiation. The sequencing strategy of chemotherapy followed by chemoradiation optimizes the impact of systemic therapy and reserves chemoradiation for those patients who are most likely to benefit. Given what we know about the genomic heterogeneity of pancreatic tumors, personalization of care should have the highest priority. Thus far, surgical pathology specimens from randomized adjuvant trials have proven to be the best source of tissue for correlative studies in pancreatic cancer.