Identification of patients with advanced pancreatic cancer who might benefit from third-line chemotherapy

Abstract

BACKGROUND

Survival rates of patients with advanced pancreatic cancer (APC) have been improved with palliative chemotherapy series. The current preferred first-line regimen consists of combination therapy of 5-fluorouracil (5-FU)/leucovorin (LV), irinotecan, and oxaliplatin (FOLFIRINOX) or gemcitabine plus albumin-bound paclitaxel (GNP). After failure of first-line chemotherapy, there are a few options for subsequent therapy including switch to the unused first-line regimen or nano-liposomal irinotecan and 5-FU/LV. However, there are limited studies on the efficacy of third-line chemotherapy after failure of second-line chemotherapy.

AIM

To identify patients with APC who might benefit from third-line chemotherapy.

METHODS

Medical records from a single tertiary hospital were retrospectively reviewed between 2012 and 2021. The study included patients with histologically or cytologically confirmed metastatic or locally APC who underwent first-line FOLFIRINOX or GNP and subsequently received third-line chemotherapy. Overall survival (OS) after diagnosis and OS after third-line chemotherapy (OS3) were defined as the interval from the diagnosis to all-cause death and the time between the initiation of the third-line chemotherapy to all-cause death, respectively.

RESULTS

A total of 141 patients were enrolled. The median patient age at diagnosis was 61.8 years (36.0-86.0), and 54.9% were male. The first-line regimen was FOLFIRINOX (67.4%) or GNP (32.6%). The second-line regimen was FOLFIRINOX (27.0%), GNP (52.5%), or other (20.6%). The median OS was 19.0 months, and the median OS3 and progression-free survival after third-line treatment were 15.3 and 7.3 weeks, respectively. With regard to the best tumor response during third-line chemotherapy, 1.4% had partial response, 24.8% had stable disease, and 59.6% had progressive disease. The following clinical factors before third-line chemotherapy affected OS3: Good performance status (PS), serum carbohydrate antigen 19-9 (CA19-9) level < 1000 U/mL, duration of second-line chemotherapy ≥ 19 weeks, and no peritoneal seeding.

CONCLUSION

This study identified that patients with good PS, CA19-9 < 1000 U/mL, second-line chemotherapy ≥ 19 weeks, and no peritoneal seeding before starting third-line treatment may benefit more from third-line chemotherapy.

Keywords: Pancreatic cancer; Chemotherapy; Survival; Performance status; Carbohydrate antigen 19-9

Core Tip: This study retrospectively analyzed 141 patients with advanced pancreatic cancer treated between 2012 and 2021, who underwent first-line oxaliplatin or gemcitabine plus nab-paclitaxel, followed by third-line chemotherapy. The median overall survival was 19 months, with 15.3 weeks after third-line treatment. The study identified that patients with good performance status, carbohydrate antigen 19-9 < 1000 U/mL, second-line chemotherapy ≥ 19 weeks, and no peritoneal seeding before starting third-line treatment had better outcomes regardless of the third-line regimen. These findings suggest that such patients may benefit more from third-line chemotherapy in spite of unsatisfactory treatment results from all patients.