KEY TAKEAWAYS
- A phase II clinical trial (SWOG S1505) assessed the impact of chemotherapy dose reductions or missed cycles in patients with resectable PDAC.
- DD as a predictor of OS at two-time points revealed a strong correlation between higher DD and improved OS in patients with resectable PDAC.
- No Significant Impact on Pathological Response in Pancreatic Cancer Treatments.
While chemotherapy is a cornerstone of multimodality treatment for resectable pancreatic ductal adenocarcinoma (PDAC), evaluating the impact of chemotherapy dose reductions or missed cycles on survival remains challenging due to the limited number of clinical trials specifically designed to assess the prognostic value of this crucial factor.
A study analyzed data from a randomized phase II clinical trial (SWOG S1505) to explore the impact of chemotherapy dose reductions or missed cycles on survival in resectable PDAC.
In this randomized, phase II study (SWOG S1505, NCT02562716), perioperative chemotherapy was administered, consisting of 12 weeks of neoadjuvant and 12 weeks of adjuvant treatment with mFOLFIRINOX or gemcitabine/nab-paclitaxel for resectable PDAC. Dose density (DD) was previously defined as the estimated percentage of chemotherapy dose received compared to the total planned per protocol.
Thresholds were set based on published studies and balanced sample sizes across treatment arms. Cox regression analysis was supervised on overall survival (OS) according to DD in patients who were alive at two landmark time points: after surgery (among those who completed surgery) and at 40 weeks (when protocol therapy was intended to be completed).
A total of 103 eligible patients were enrolled, with a median age of 64 years. Among them, 81% underwent pancreaticoduodenectomy, 15% underwent distal pancreatectomy, and 3% underwent total pancreatectomy. In the subgroup of 73 patients who had surgery, the median neoadjuvant chemotherapy DD was 89%.
Patients with a DD ≥ 85% showed a higher median OS from surgery (38.1 vs. 17.2 months, p = 0.039) than those with a DD < 85%. Of the 82 patients surviving to 40 weeks post-randomization, 67 underwent surgery, and 58 initiated adjuvant chemotherapy.
The median DD for all perioperative chemotherapy was 67%. Notably, DD was significantly higher for neoadjuvant than adjuvant therapy (83% vs. 58%, p < 0.001). In this cohort, a DD ≥ 70% correlated with a better median OS from 40 weeks post-randomization (32.2 vs. 14.0 months, p = 0.017). DD did not exhibit a significant association with pathologic response, margin status, or lymph node negativity. Additionally, there were no significant differences in DD between the mFOLFIRINOX and gemcitabine/nab-paclitaxel arms.
Higher chemotherapy DD was associated with significantly improved overall survival in resectable PDAC. Patients receiving ≥ 85% DD preoperatively and/or ≥70% DD preoperatively had superior survival outcomes.
Source: https://ascopubs.org/doi/10.1200/JCO.2023.41.16_suppl.4158
Clinical Trial: https://www.clinicaltrials.gov/study/NCT02562716
Sameer H. Patel, Sarah Colby, Davendra Sohal, Katherine A Guthrie, Lisa A. Kachnic, E. Gabriela Chiorean, Andrew M. Lowy, Flavio G Rocha, Philip Agop Philip, Syed Ahmad. DOI 10.1200/JCO.2023.41.16_suppl.4158, J Clin Oncol 41, 2023 (suppl 16; abstr 4158).
