From the Guidelines
Recent advances in pancreatic ductal adenocarcinoma (PDAC) have significantly improved treatment options, with neoadjuvant therapy emerging as a crucial approach to downstage borderline resectable tumors and improve outcomes. The use of neoadjuvant therapy, particularly in patients with high-risk features, has been supported by recent guidelines, including the NCCN Clinical Practice Guidelines in Oncology 1. According to these guidelines, neoadjuvant therapy should be administered at or coordinated through a high-volume center, and upfront resection in patients with borderline resectable disease is no longer recommended.
Key benefits of neoadjuvant therapy include increasing the likelihood of margin-negative resection, downsizing tumors, and treating micrometastases at an earlier stage 1. Acceptable regimens for neoadjuvant therapy include FOLFIRINOX, gemcitabine/albumin-bound paclitaxel, and gemcitabine/cisplatin, particularly for patients with BRCA1/2 or other DNA repair mutations. The ESPAC-4 trial, a multicenter, international, open-label randomized controlled phase III trial, demonstrated the efficacy of adjuvant combination chemotherapy with gemcitabine and capecitabine in improving median survival to 28.0 months, compared to 25.5 months with gemcitabine alone 2.
Neoadjuvant Therapy Regimens
- FOLFIRINOX: 5-fluorouracil, leucovorin, irinotecan, and oxaliplatin
- Gemcitabine/albumin-bound paclitaxel
- Gemcitabine/cisplatin (for patients with BRCA1/2 or other DNA repair mutations)
Adjuvant Therapy
- The doublet regimen of gemcitabine and capecitabine is preferred in the absence of concerns for toxicity or tolerance
- Monotherapy with gemcitabine or fluorouracil plus folinic acid can be offered as an alternative
- Adjuvant treatment should be initiated within 8 weeks of surgical resection, assuming complete recovery 2
Future Directions
- Early detection strategies using liquid biopsies and advanced imaging techniques are being developed to identify PDAC at earlier, more treatable stages
- Molecular profiling has enabled more personalized treatment approaches, with targeted therapies now available for specific genetic alterations
- Immunotherapy has shown promise in microsatellite instability-high tumors, with pembrolizumab now approved for this subset.
From the Research
Recent Advances in Pancreatic Ductal Adenocarcinoma (PDAC)
- The implementation of contemporary chemotherapy regimens, such as FOLFIRINOX and gemcitabine with nab-paclitaxel, has improved overall survival in patients with metastatic PDAC 3.
- A single center experience with resectable PDAC highlighted the limitations of the surgery-first approach, with a median survival of 18.4 months and 5-year overall survival of 13% 4.
- Adjuvant treatment of surgically resectable PDAC has evolved, with combination chemotherapy and neoadjuvant chemoradiation therapy showing promise in improving outcomes 5.
- The optimal treatment algorithm for metastatic PDAC is still unclear, but chemotherapy remains the mainstay of treatment, with selected patients receiving second-line treatment with moderate clinical benefit 6.
- Neoadjuvant therapy is emerging as a key strategy in PDAC management, with recent advances in treatment protocols showing promising results in increasing the proportion of patients eligible for surgery and improving overall survival rates 7.
Treatment Options
- FOLFIRINOX and gemcitabine with nab-paclitaxel are now integral to neoadjuvant therapy strategies, offering improved response rates and survival benefits compared to traditional regimes 3, 7.
- Chemotherapy, radiotherapy, or a combination of both are used in neoadjuvant therapies to reduce tumor size and increase the feasibility of complete surgical resection 7.
- Second-line treatment options, such as nanoliposomal irinotecan plus 5-fluouracil and leucovorin, are available for selected patients progressing to first-line therapy 6.
Future Directions
- Ongoing research is needed to optimize treatment regimens, minimize adverse effects, and identify patient populations that would benefit most from neoadjuvant therapies 7.
- Future clinical trials will help define a standard algorithm for PDAC treatment, taking into account sequential treatment as a new paradigm in PDAC 6.