Perioperative Integration With Medical Oncologists: Neoadjuvant and Adjuvant Therapy

Surgical resection has curative potential in some patients with resectable intrahepatic cholangiocarcinoma (iCCA); however, frequency of recurrence is high, underscoring the need for novel approaches. In order to improve patient outcomes, the roles of neoadjuvant and adjuvant therapy are being explored in patients with potentially resectable iCCA. At the 5th annual CCA Summit meeting, the perioperative integration of neoadjuvant and adjuvant therapy with medical oncologists was discussed by Cristine R. Ferrone, MD.¹

Surgical resection is the treatment of choice in resectable patients with good performance status; it is a minimally invasive approach associated with a 30-day mortality rate of 2.5% and a 30-day major morbidity rate of 19.6%. Adjuvant chemotherapy following curative-intent resection in biliary tract cancer resulted in significant improvement in recurrence-free survival and overall survival outcomes compared to surgery alone.¹ In the BILCAP trial, median overall survival was 49.6 months with adjuvant capecitabine versus 36.1 months without adjuvant therapy at a median follow-up of 106 months; subgroup analysis did not demonstrate an advantage in poorly differentiated tumors or site of disease.² However, the phase 3 SWOG 1815 trial did not demonstrate a significant improvement with nab-paclitaxel plus gemcitabine/cisplatin versus gemcitabine/cisplatin alone, despite showing clinical efficacy in phase 2 trials, which underscores the importance of phase 3 randomized controlled trials.³ Dr Ferrone noted that hyperbilirubinemia does not delay therapy and that steatosis is not exacerbated by adjuvant chemotherapy.¹

Currently, there are no clinical trial data to support neoadjuvant therapy in patients with resectable iCCA.¹ In this setting, Dr Ferrone recommended that patients should only be offered neoadjuvant therapy in the context of a clinical trial. Patients with borderline or locally advanced cancers should be offered neoadjuvant therapy.¹ Among 102 patients with CCA undergoing resection (neoadjuvant, n=42; adjuvant, n=38), perioperative systemic therapy had the largest effect on positive margins and tumors >5 cm.⁴ A phase 2, single-arm, prospective, feasibility study (NEO-GAP) evaluated neoadjuvant gemcitabine/cisplatin plus nab-paclitaxel for resectable high-risk iCCA in 30 evaluable patients; 10 (33%) grade 3/4 treatment-related adverse events (most commonly neutropenia and diarrhea) were reported with neoadjuvant chemotherapy. A total of 22 patients completed all preoperative chemotherapy and underwent surgical resection, and 23% achieved an overall response rate, including a partial response rate of 23% (stable disease, 67%; progressive disease, 10%); 23 patients underwent surgical resection.⁵

These data support the continued use of surgical resection as standard of care accompanied by neoadjuvant and adjuvant therapy in the management of resectable iCCA. Given the evolving genetic treatment landscape in CCA, Dr Ferrone stressed that molecular and immune stratification should be routinely performed in iCCA.¹

Sources:

1. Ferrone CR. Perioperative integration with medical oncologists: neoadjuvant and adjuvant therapy. Presented at: 5th Annual CCA Summit Meeting, October 19-21, 2023; Scottsdale, AZ.
2. Bridgewater J, Fletcher P, Palmer DH, et al. Long-term outcomes and exploratory analyses of the randomized phase III BILCAP study. J Clin Oncol. 2022;40(18):2048-2057.
3. Shroff RT, Guthrie KA, Scott JA, et al. SWOG 1815: a phase III randomized trial of gemcitabine, cisplatin, and nab-paclitaxel versus gemcitabine and cisplatin in newly diagnosed, advanced biliary tract cancers. J Clin Onc. 2023;41(4 suppl):LBA490-LBA490.
4. Hassan H, Chakrabarti S, Zemla T, et al. Impact of perioperative chemotherapy on survival in patients with cholangiocarcinoma undergoing curative resection. Eur J Surg Oncol. 2023:106994.
5. Maithel SK, Keilson JM, Cao HST, et al. NEO-GAP: a single-arm, phase II feasibility trial of neoadjuvant gemcitabine, cisplatin, and nab-paclitaxel for resectable, high-risk intrahepatic cholangiocarcinoma. Ann Surg Oncol. 2023 Oct;30(11):6558-6566.