Second line treatment options for pancreatic cancer

ABSTRACT

Introduction: Patients with advanced pancreatic cancer (APC) refractory to first-line therapy have a dismal prognosis and limited therapeutic options, with only one option consisting of nanoliposomal irinotecan in combination with fluorouracil and folinic acid which was approved by FDA based upon results of the phase III NAPOLI-1 study.

Areas covered: We performed a literature search for relevant published clinical trials, abstracts of trials in progress and ongoing or planned trials for the second line treatment of APC using Pubmed.com, ClinicalTrials.gov and American Society of Clinical Oncology (ASCO) abstract search as sources. We present an in-depth analysis of the phase I-III clinical trials determining the role and efficacy of second-line treatment in patients with APC. We also describe ongoing studies and rationale for future investigation.

Expert opinion: Despite advances in first-line therapy such as gemcitabine/nab-paclitaxel and FOLFIRINOX in APC, median overall survival remains less than 12 months, highlighting the need to develop second-line therapies. In order to establish much needed effective second-line treatment options, we need cooperative efforts among institutions and community practices in enrolling these refractory patients in clinical trials. It should be emphasized that in addition to chemotherapy options, all patients should have the opportunity to consult with nutritionist, social worker and palliative care health providers to assist with goals of care, symptom management and end of life discussions.

KEYWORDS:

• Irinotecan liposome injection
• gemcitabine
• nanoliposomal irinotecan
• pancreatic cancer
• oxaliplatin
• 5-fluorouracil
• immunotherapy
• ruxolitinib
• vaccines
• stroma

Article highlights

• Pancreatic ductal adenocarcinoma is a leading cause of deaths due to cancer with a 5-year survival rate of <5%.

• Despite advances in first-line therapy such as gemcitabine/nab-paclitaxel and FOLFIRINOX in APC, median overall survival remain less than 12 months, highlighting the need to develop second-line therapies.

• Recent studies have shown positive effect on overall survival in the second-line setting whose tumor progresses past first-line treatment.

• The increased delivery of 2nd line chemotherapy to patients with advanced pancreatic cancer who maintained performance status may offer a survival benefit for this population.

• Nanoliposomal irinotecan is the first agent approved by FDA when given in combination with 5-FU and folinic acid in the second-line treatment of patients with pancreatic cancer after gemcitabine fails.

• The assessment of a patient’s symptom burdens, performance status and associated comorbidities, psychosocial milieu and goals of care are all important considerations in selecting the most appropriate first and second-line therapy.

• Current data suggests that certain characteristics of patients and or disease were independent prognostic factors for subsequent OS for second line therapy in these patients:

  • (10) Age

  • (11) smoking status

  • (12) presence of ascites

  • (13) liver metastases

  • (14) ECOG PS

  • (15) Pain

  • (16) Jaundice

  • (17) Duration of first-line chemotherapy

  • (18) Type of second line therapy

• An open communication between physician and patient, with the mutual understanding that APC is presently an incurable disease is essential.

• Regardless of therapy chosen, adjunctive support with symptom focused management, nutritionist consultation, and involvement of colleagues in the areas of palliative services all have an important role in providing patients with a comprehensive plan of care that seeks to optimize quality of life in this devastating disease.

• There is intense need to research to identify biomarkers to better stratify patients based on risk of aggressive disease and identify those who will respond to treatment.

• In order to establish a much needed effective 2nd line treatment options for advanced pancreatic cancer, we need cooperative efforts among institutions and community practices in enrolling gemcitabine refractory patients in clinical trials.

• The main findings on the second line allow optimism and set the platform of new prospective and randomized trials that will confirm the above data.

This box summarizes key points contained in the article.

Declaration of interest

MW Saif has received a grant from Merrimack for research funding. In addition, he has been selected for Speaker bureau of Celgene and Merrimack. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Additional information

Funding

This paper was not funded