The efficacy and safety profile of third-line treatment in patients with metastatic pancreatic adenocarcinoma

Background

For metastatic pancreatic ductal adenocarcinoma (mPDAC), there are no established third-line chemotherapy options. We examined the efficacy and safety of third-line chemotherapy in patients with mPDAC in real-world practice.

Methods

We retrospectively analyzed 257 patients with mPDAC and progressive disease after first-line treatment with gemcitabine-based regimens and second-line treatment with liposomal irinotecan plus 5-fluorouracil and leucovorin at five Taiwanese medical centers from 2018 to 2022. Treatment efficacy and toxicity were analyzed in 77 of 257 patients receiving third-line treatment subsequently. We performed univariate and multivariate analyses to identify prognostic factors for overall survival (OS) in patients receiving third-line treatment.

Results

Patients receiving third-line treatment had a median OS of 4.5 months (95 % confidence interval [CI], 3.6–5.4), compared to 1.6 months (95 % CI, 1.3–1.9) for those who did not. Independent poor prognostic factors for OS included the absence of previous pancreatectomy (adjusted hazard ratio [aHR] 3.03, 95 % CI, 1.30–7.14, P = 0.001), an ECOG score of ≥2 ((aHR 9.81, 95 % CI 4.34–22.1, P < 0.001), and progressive disease response during second-line treatment (aHR 1.90, 95 % CI 1.21–8.91, P = 0.020, P = 0.020). Median OS for patients with none, one, two, and three poor prognostic factors were 15.9 (95 % CI, 12.3–19.6), 7.0 (2.6–13.3), 4.4 (3.5–5.2), and 2.0 (1.7–2.2) months, respectively. 43 of 77 patients (56 %) experienced at least one grade 3 or 4 toxicity.

Conclusion

In real-world settings, patients with mPDAC receiving third-line chemotherapy may have a moderate survival advantage, although clinicians should carefully select patients owing to high incidence of grade 3/4 toxicities.