For patients with localized intrahepatic cholangiocarcinoma (iCCA), surgical resection holds curative potential for only 30% to 35% of patients due to its high rate of recurrence. A previous study of gemcitabine/cisplatin/nab-paclitaxel combination chemotherapy (GAP) showed a partial response rate of 45% in locally advanced, unresectable biliary cancer, and 20% of patients who were previously inoperable underwent margin-negative resection.1 The NEO-GAP trial, a multi-institutional, prospective, single-arm, phase 2 study, was conducted to evaluate the GAP regimen in the neoadjuvant setting for patients with resectable but high-risk iCCA.
This feasibility study enrolled patients with resectable high-risk disease (defined as solitary tumor >5 cm, multiple tumors, presence of major vascular invasion, or lymph node involvement). Prior to surgical resection, eligible patients received 4 cycles of the GAP regimen (gemcitabine 800 mg/m2, cisplatin 25 mg/m2, nab-paclitaxel 100 mg/m2 on days 1 and 8 every 21 days). The primary end point was completion of all therapy, including both preoperative chemotherapy and resection. Secondary end points were tolerability, radiologic response, and microscopically margin-negative (R0) resection rate.
A total of 30 patients were enrolled in the study (September 2018-September 2021) and received treatment. The median age of the study population was 61.2 years, and most patients were men (60%). Of the 30 patients, 22 (73%; P = .0106) completed all preoperative chemotherapy and underwent surgical resection.
Grade 3/4 treatment-related adverse events (TRAEs) were reported in 10 (33%) patients; of these, the most common TRAEs were neutropenia and diarrhea. Overall, 50% of the study population required ≥1 dose reductions.
In terms of efficacy, a partial response was achieved by 23% of patients; the disease control rate was 90%, including stable disease in 67% of patients. Of the 22 patients who underwent surgical resection, 2 had minor postoperative complications. Most patients achieved lymph node–negative disease (64%), and 73% had R0 margin status. No treatment-related deaths occurred.
Of the patients who underwent resection following the GAP regimen, the median size of the largest tumor was 5.5 cm; median number of tumors was 3.5. The median length of hospital stay was 4 days.
Based on these results, the researchers concluded that neoadjuvant GAP is feasible and safe prior to curative-intent surgical resection in patients with iCCA and does not adversely affect perioperative outcomes.
Source: Maithel SK, Javle MM, Mahipal A, et al. NEO-GAP: a phase II single-arm prospective feasibility study of neoadjuvant gemcitabine/cisplatin/nab-paclitaxel for resectable high-risk intrahepatic cholangiocarcinoma. Abstract 4097.
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