Impact of Nab–Paclitaxel-based Second-line Chemotherapy in Metastatic Pancreatic Cancer

Abstract

OS (7.5 vs. 4.7 months; HR=0.67, p=0.05). Multivariate analyses adjusted for age showed a significantly improved PFS (adjusted HR=0.60, p=0.04) and a suggestion of improved OS (adjusted HR=0.67, p=0.05) Pancreatic ductal adenocarcinoma (PDAC) is a lethal cancer and is the fourth leading cause of cancer-related mortality in the United States (US) (1). In 2017 alone, 53,670 cases of PDAC are expected, resulting in approximately 43,090 deaths in the US (2). The median overall survival (OS) of patients with PDAC is 20% at 1 year and 8% at 5 years (3). Despite recent progress, there is a clear need to improve systemic treatments for PDAC. Recently, nab-paclitaxel (NP) in combination with gemcitabine (GA) was shown to lead to a clinically meaningful and significant improvement in the median OS and median progression-free survival (PFS) when compared with gemcitabine alone (4). This has led to the approval of GA as a first-line treatment for PDAC similar to FOLFIRINOX (folinic acid, 5-fluorouracil, irinotecan and oxaliplatin), the only other first-line treatment for patients with metastatic PDAC (5).In clinical practice, many patients may receive FOLFIRINOX as first-line treatment and GA as the secondline treatment especially in the US (6). Many factors influence the decision to select between FOLFIRINOX and GA including age, performance status, associated comorbidities and potential toxicity (7). FOLFIRINOX is often chosen for patients with good performance status, age ≤75 years and lack of or controlled comorbidities (7,8). Usually in this scenario, GA is the preferred second-line treatment after progression on FOLFIRINOX in the absence of prospective data. Alternatively, 5-fluorouracil-based second-line therapy in combination with nanoparticle liposomal irinotecan (9) or oxaliplatin (10, 11) has shown OS benefit in second-line treatment. Interestingly, up to 50% of patients with PDAC may be eligible for second-line chemotherapy (12, 13). 5533

Nab-paclitaxel and gemcitabine or FOLFIRINOX as first-line treatment in patients with unresectable adenocarcinoma of the pancreas: does sequence matter?

“…There is limited evidence in the literature regarding whether the choice of first-line treatment and sequence is important for outcome in patients with pancreatic cancer. However, there are reports, mostly case studies, summarizing the experience of second-line nabPGem after initial treatment with FOLFIRINOX [27–31]. The largest report is from Portal and colleagues, who enrolled 57 patients [32].…”

Overall survival of patients with recurrent pancreatic cancer treated with systemic therapy: a retrospective study

“…We conducted a retrospective study using Indiana University’s Institution Review Board (IRB) approved database of patients with PDAC [14]. Information in this database are gathered retrospectively on an ongoing basis and stored in the OnCore™ Enterprise Research System, in compliance with institutional guidelines.…”

High G2M Pathway Score Pancreatic Cancer is Associated with Worse Survival, Particularly after Margin-Positive (R1 or R2) Resection

“…Several therapies focus on inactivating the checkpoint in order to force cells with excess DNA damage to proceed through mitosis and induce cell death. For example, the taxanes arrest cells at the G2M phase of the cell cycle that demonstrated significant impact against many solid tumors, such as gastric cancer [ 11 ], lung cancer [ 12 ], breast cancer [ 13 , 14 ], and pancreatic cancer [ 15 , 16 ]. Thus, we sought to quantify the amount of G2M checkpoint pathway activity.…”