Metastatic Pancreatic Adenocarcinoma (PDAC)

Front-line Treatment for Metastatic Pancreatic Adenocarcinoma (PDAC)

Patients with poor performance status ought to be offered the best supportive care. In younger patients with good performance status, options forfirst-line chemotherapy that have emerged in more recent studies include FOLFIRINOX16and gemcitabine in combination with nab-paclitaxel. 17This is based on the PRODIGE16and MPACT17trials respectively, first-line radiochemotherapies (RCTs) showing overall survival benefits when compared to the existing standard of gemcitabine monotherapy.18

FOLFIRINOX has shown an improvement in both median progression-free survival (PFS) (6.4 months vs 3.3 months, P <0.001) and median OS (11.1 months vs 6.8 months, P <0.001). The rates of grade III or IV toxicities were higher in the FOLFIRINOX arm, in particular 45.7% for neutropenia, though there were no toxic deaths reported. In fact, the patients in the FOLFIRINOX arm had an improved quality of life comparatively.18The toxicities of FOLFIRINOX could be managed with supportive measures such as growth factor support.

The MPACT trial17showed that the addition of nabpaclitaxel to gemcitabine demonstrated improved median OS (8.5 months vs 6.7 months; P <0.0001), median PFS (5.5 months vs 3.7 months; P <0.001) and improved overall response rate (ORR) (23% vs 7%; P <0.001). The common grade III or IV adverse events attributable to nab-paclitaxel were neutropenia (38%), fatigue (17%), and neuropathy (17%). For older patients and individuals who are unable to tolerate combination therapy, it is reasonable to consider monotherapy with either gemcitabine or S-1.19-20

Addition of Targeted Therapy to Systemic Chemotherapy

There is currently no evidence to support the use of targeted therapy with bevacizumab or cetuximab in combination with chemotherapy in the first-line treatment of metastatic pancreatic carcinoma.

Second-line Treatment

In the second-line setting, for patients with good performance status, fluoropyrimidine-based chemotherapy is recommended for patients who had previouslybeen treated with gemcitabine based therapy21-26or gemcitabine-based therapy if previously treated with fluoropyrimidine-based therapy. 26

A systemic review of clinical trials done in the second-line setting revealed that there is limited data but possible advantage of second-line treatment over best supportive care.26Third-line Treatment Patients who have progressed beyond 2 or more lines of treatment are recommended for enrollment in clinical trials if they still have good performance status.

Recommendations for Metastatic Pancreatic Cancer

1. Best supportive care ought to be considered for patients with poor performance status.

2. Systemic chemotherapy is recommended for patients with good performance status. First-line chemotherapy with FOLFORINOX or combination gemcitabine and abraxane is preferred.

3. In the second-line setting, the recommendation is fluoropyrimidine-based chemotherapy if previously treated with gemcitabine-based therapy or gemcitabinebased therapy if previously treated with fluoropyrimidinebased therapy.

4. After second-line therapy, participation in clinical trials is recommended if available. All recommendations were unanimously agreed upon.