TY - JOUR
T1 - A Phase II Randomized Trial of Panitumumab, Erlotinib, and Gemcitabine Versus Erlotinib and Gemcitabine in Patients with Untreated, Metastatic Pancreatic Adenocarcinoma
T2 - North Central Cancer Treatment Group Trial N064B (Alliance)
AU - Halfdanarson, Thorvardur R.
AU - Foster, Nathan R.
AU - Kim, George P.
AU - Meyers, Jeffrey P.
AU - Smyrk, Thomas C.
AU - McCullough, Ann E.
AU - Ames, Matthew M.
AU - Jaffe, Jeffrry P.
AU - Alberts, Steven R.
N1 - Funding Information:
The following institutional networks participated in this study: Colorado Cancer Research Program NCORP (National Cancer Institute [NCI] Community Oncology Research Program), Denver, CO, Keren Sturtz, UG1CA189805; Dayton NCI Community Oncology Research Program, Dayton, OH, Howard Gross, UG1CA189957; Geisinger Cancer Institute NCI Community Oncology Research Program, Danville, PA, Srilatha Hosur, UG1CA189847; Hawaii Minority Underserved NCORP, Honolulu, HI, Jeffrey Berenberg, UG1CA189804; Iowa-Wide Oncology Research Coalition NCORP, Des Moines, IA, Robert Behrens, UG1CA189816; Mayo Clinic LAPS, Rochester, MN, Steven Alberts, U10CA180790; Metro Minnesota Community Oncology Research Consortium, Saint Louis Park, MN, Daniel Anderson, UG1CA189863; Michigan Cancer Research Consortium NCORP, Ann Arbor, MI, Philip Stella, UG1CA189971; Missouri Valley Cancer Consortium CCOP (Community Clinical Oncology Program), Omaha, NE, Gamini Soori, U10CA063849; Montana Cancer Consortium NCORP, Billings, MT, Benjamin Marchello, UG1CA189872; Northern Indiana Cancer Research Consortium, South Bend, IN; Michael Method, U10CA086726; Ochsner NCI Community Oncology Research Program, New Orleans, LA, John Cole, UG1CA189870; Pacific Cancer Research Consortium NCORP, Seattle, WA, Alison Conlin, UG1CA189953; Rapid City Regional Hospital, Rapid City, SD, Joshua Lukenbill; Sanford NCI Community Oncology Research Program of the North Central Plains, Sioux Falls, SD, Preston Steen, UG1CA189825; Southeast Clinical Oncology Research Consortium NCORP, Winston-Salem, NC, James Atkins, UG1CA189858; Toledo Clinic Cancer Centers-Toledo, Toledo, OH, Rex Mowat; Toledo Community Hospital Oncology Program CCOP, Toledo, OH, Rex Mowat; Wichita NCI Community Oncology Research Program, Wichita, KS, Shaker Dakhil, UG1CA189808; and Wisconsin NCI Community Oncology Research Program, Marshfield, WI, Anthony Jaslowski, UG1CA189956.
Publisher Copyright:
© AlphaMed Press; the data published online to support this summary are the property of the authors
PY - 2019/5
Y1 - 2019/5
N2 - Lessons Learned: Dual epidermal growth factor receptor (EGFR)-directed therapy with erlotinib and panitumumab in combination with gemcitabine was superior to gemcitabine and erlotinib, but the clinical relevance is uncertain given the limited role of gemcitabine monotherapy. A significantly longer overall survival was observed in patients receiving the dual EGFR-directed therapy. The dual EGFR-directed therapy resulted in increased toxicity. Background: Gemcitabine is active in patients with advanced pancreatic adenocarcinoma. The combination of erlotinib, an oral epidermal growth factor receptor (EGFR) inhibitor, and gemcitabine was shown to modestly prolong overall survival when compared with gemcitabine alone. The North Central Cancer Treatment Group (now part of Alliance for Clinical Trials in Oncology) trial N064B compared gemcitabine plus erlotinib versus gemcitabine plus combined EGFR inhibition with erlotinib and panitumumab. Methods: Eligible patients with metastatic adenocarcinoma of the pancreas were randomized to either gemcitabine 1,000 mg/m2 on days 1, 8, and 15 of a 28-day cycle with erlotinib 100 mg p.o. daily (Arm A) or the same combination with the addition of panitumumab 4 mg/kg on days 1 and 15 of a 28-day cycle (Arm B). The primary endpoint of the trial was overall survival. Secondary endpoints included progression-free survival, the confirmed response rate, and toxicity. Comparison between arms for the primary endpoint was done with a one-sided log-rank test, and a p value less than.20 was considered statistically significant. Response rate comparison was done with Fisher's exact test. All other reported p values are two-sided. Results: A total of 92 patients were randomized, 46 to each arm. The median overall survival was 4.2 months in Arm A and 8.3 months in Arm B (hazard ratio, 0.817; 95% confidence interval [CI], 0.530–1.260; p =.1792). The progression-free survival was 2.0 months in Arm A and 3.6 months in Arm B (hazard ratio, 0.843; 95% CI, 0.555–1.280; p =.4190). A partial confirmed response was seen in 8.7% of patients on Arm A and 6.5% on Arm B (p =.9999). No patients had a complete response. Grade 3 and higher nonhematologic toxicities were more common in patients on Arm B compared with those on Arm A (82.6% vs. 52.2%; p =.0018). Conclusion: Dual EGFR-directed therapy resulted in a significant prolongation of overall survival in patients with advanced adenocarcinoma of the pancreas but was associated with substantially increased toxicities. Dual EGFR-directed therapy in combination with gemcitabine alone cannot be recommended for further study, as single-agent gemcitabine is no longer considered an appropriate therapy for otherwise fit patients with metastatic pancreatic cancer.
AB - Lessons Learned: Dual epidermal growth factor receptor (EGFR)-directed therapy with erlotinib and panitumumab in combination with gemcitabine was superior to gemcitabine and erlotinib, but the clinical relevance is uncertain given the limited role of gemcitabine monotherapy. A significantly longer overall survival was observed in patients receiving the dual EGFR-directed therapy. The dual EGFR-directed therapy resulted in increased toxicity. Background: Gemcitabine is active in patients with advanced pancreatic adenocarcinoma. The combination of erlotinib, an oral epidermal growth factor receptor (EGFR) inhibitor, and gemcitabine was shown to modestly prolong overall survival when compared with gemcitabine alone. The North Central Cancer Treatment Group (now part of Alliance for Clinical Trials in Oncology) trial N064B compared gemcitabine plus erlotinib versus gemcitabine plus combined EGFR inhibition with erlotinib and panitumumab. Methods: Eligible patients with metastatic adenocarcinoma of the pancreas were randomized to either gemcitabine 1,000 mg/m2 on days 1, 8, and 15 of a 28-day cycle with erlotinib 100 mg p.o. daily (Arm A) or the same combination with the addition of panitumumab 4 mg/kg on days 1 and 15 of a 28-day cycle (Arm B). The primary endpoint of the trial was overall survival. Secondary endpoints included progression-free survival, the confirmed response rate, and toxicity. Comparison between arms for the primary endpoint was done with a one-sided log-rank test, and a p value less than.20 was considered statistically significant. Response rate comparison was done with Fisher's exact test. All other reported p values are two-sided. Results: A total of 92 patients were randomized, 46 to each arm. The median overall survival was 4.2 months in Arm A and 8.3 months in Arm B (hazard ratio, 0.817; 95% confidence interval [CI], 0.530–1.260; p =.1792). The progression-free survival was 2.0 months in Arm A and 3.6 months in Arm B (hazard ratio, 0.843; 95% CI, 0.555–1.280; p =.4190). A partial confirmed response was seen in 8.7% of patients on Arm A and 6.5% on Arm B (p =.9999). No patients had a complete response. Grade 3 and higher nonhematologic toxicities were more common in patients on Arm B compared with those on Arm A (82.6% vs. 52.2%; p =.0018). Conclusion: Dual EGFR-directed therapy resulted in a significant prolongation of overall survival in patients with advanced adenocarcinoma of the pancreas but was associated with substantially increased toxicities. Dual EGFR-directed therapy in combination with gemcitabine alone cannot be recommended for further study, as single-agent gemcitabine is no longer considered an appropriate therapy for otherwise fit patients with metastatic pancreatic cancer.
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U2 - 10.1634/theoncologist.2018-0878
DO - 10.1634/theoncologist.2018-0878
M3 - Article
C2 - 30679315
AN - SCOPUS:85060586680
VL - 24
SP - 589-e160
JO - Oncologist
JF - Oncologist
SN - 1083-7159
IS - 5
ER -