A phase 1b study of erlotinib in combination with gemcitabine and nab-paclitaxel in patients with previously untreated advanced pancreatic cancer: an Academic Oncology GI Cancer Consortium study

Purpose Addition of either nab-paclitaxel or erlotinib to gemcitabine to treat advanced pancreatic cancer has demonstrated overall survival benefit. This study was conducted to evaluate the tolerability and safety of combining all three drugs and assess preliminary evidence of efficacy. Methods In this open-label, phase 1b study, patients with previously untreated, advanced pancreatic cancer were treated in 28-day cycles with intravenous gemcitabine/nab-paclitaxel on days 1, 8, and 15, and once daily oral erlotinib. A standard “3 + 3” design was used. Dose level 1 (DL1) for gemcitabine (mg/m 2 )/nab-paclitaxel (mg/m 2 )/erlotinib (mg) was 1000/125/100, respectively, with de-escalation to DL−1 (1000/100/100), DL−2b (1000/75/100), and DL−3 (1000/75/75). The maximum tolerated dose (MTD) was defined by occurrence of dose-limiting toxicity (DLT) in ≤1 of six patients within the first cycle. Efficacy was assessed with CT scans performed at two-cycle intervals. Results Nineteen patients were enrolled. DLTs occurred in two patients at DL1, three patients at DL−1, two patients at DL−2b, and one patient at DL−3. The MTD for the combination of gemcitabine/nab-paclitaxel/erlotinib was DL−3 (1000/75/75). In analyses of efficacy among 14 evaluable patients, partial responses were observed in four of six patients at DL1, one of two patients at DL−2b, and two of six patients at DL−3. Conclusion The addition of erlotinib to gemcitabine and nab-paclitaxel is not tolerable at standard single-agent dosing of all drugs. However, significant clinical activity was noted, even at DL−3. Further study of the combination will need to incorporate reduced dosing.