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Erlotinib plus gemcitabine compared to gemcitabine alone in patients with advanced pancreatic cancer.  A phase III trial of the National Cancer Institute of Cancada Clinical Trials Group (NCIC-CTG)

Reviewer: Ryan Smith , MD
OncoLink
Ultima Vez Modificado: 15 de mayo del 2005

Presenter: M.J. Moore
Presenter's Affiliation: NCIC
Type of Session: Plenary

Background

• Advanced and metastatic pancreatic cancer has an extremely poor prognosis, with median survival times between 4-6 months.
• Multiple attempts at combination chemotherapy have shown no efficacy
• Attempts at targeted agents have also been negative trials
• Targeting the epidermal growth factor receptor (EGFR) is a logical choice, as overexpression is commonly seen
• Erlotinib is a small molecule inhibitor of the EGFR, with preclinical studies showing growth inhibition of pancreatic tumor cell lines

Materials and Methods

• Eligible patients included those with advanced or metastatic pancreatic cancer who had received no prior systemic therapy other than chemotherapy concurrent with radiation
• Patients were randomized to receive either gemcitabine + erlotinib vs. gemcitabine + placebo
• Dosages were gemcitabine 1000 mg/m2 IV weekly for 7/8 weeks followed by weekly for 3/4 weeks and erlotinib initially at a dose of 100 mg per day (521 patients) or 150 mg per day (48 patients)
• Primary endpoint was overall survival, statistically powered to detect a 33% increase

Results

• 569 patients were randomized (285 erlotinib arm and 284 control arm)
• 75% had metastatic disease and 80% had a performance status of 0-1
• Median survival times (MST) were 5.9 months (control) vs. 6.4 months (erlotinib) with 1 year overall survival of 17% (control) vs. 24% (erlotinib) (p=.025)
• Progression free survival was 3.6 months (control) vs. 3.8 months (erlotinib) (p=.003)
• Grade 3 and 4 adverse effects were similar, but there were an excess of grade 1 and 2 toxicities in the erlotinib arm, most notably due to skin rash (72% vs. 29%)
• Only difference in quality of life scores was with respect to diarrhea in favor of the control arm
• Increased response and survival was not correlated with EGFR status
• Overall survival did correlate with skin rash: Grade 2 (MST 10.5 months), grade 1 (MST 5.8 months), grade 0 (MST 5.3 months)

Author's Conclusions

• This is the first trial to show a targeted agent with a survival benefit in pancreatic cancer
• Overall survival and progression free survival were both improved
• There is increased but tolerable toxicity associated with erlotinib
• The presence of a skin rash due to therapy denoted a better prognosis

Clinical/Scientific Implications