ORLANDO — Adjuvant therapy with gemcitabine (Gemzar) nearly doubled disease-free survival following surgery for pancreatic cancer in a phase III trial reported at the annual meeting of the American Society of Clinical Oncology.
Peter Neuhaus, M.D., reported that 179 patients given 6 months of gemcitabine chemotherapy went a median of 14.2 months before their disease recurred. In a control group of 177 patients, relapses occurred a median 7.5 months after surgery.
“For me as a surgeon, it is a milestone in the treatment of these patients because we have so long waited for a real improvement,” said Dr. Neuhaus of the Charité University Medical School in Berlin.
Earlier, he told reporters at a press briefing that this was the first prospective, randomized, and controlled trial to clearly show that adjuvant chemotherapy will help pancreatic cancer patients after surgery.
“Gemcitabine may become the standard of care for adjuvant treatment of pancreatic cancer,” he said during his presentation, predicting that favorable 3-year and 5-year survival rates will be reported with longer follow-up.
The chemotherapy drug is usually given to patients with inoperable, advanced disease. It is the only drug approved by the U.S. Food and Drug Administration for treatment of pancreatic cancer.
The investigators recruited patients with resectable disease at 88 cancer centers in Germany and Austria from July 1998 to December 2004. Participants were randomly assigned to the control or chemotherapy groups 22–24 days after surgery, creating similar cohorts with an average age of 61–62 years and slightly more men than women. In both arms, 86% of patients had stage T3 or T4 disease, and nearly three-quarters were lymph node positive. More than 80% had an R0 resection margin, and the rest were R1, because patients with more residual disease were excluded.
Patients in the adjuvant therapy arm received 1 g/m
Dr. Neuhaus reported that median disease-free survival with gemcitabine therapy was 19.3 months for node-negative patients and 13.1 months for node-positive patients. In the control group, median disease-free survival was 11.2 months for node-negative patients and 7 months for node-positive patients.
“We go one stage up in prognosis for survival of our patients,” Dr. Neuhaus said, describing the benefit to node-positive patients as one of the most striking outcomes of the study. Toxicity was low and was less than expected, he added. The most common grade 3 and 4 events with gemcitabine were low white blood cell count (8.4%), low platelet count (2.8%), nausea (4.5%), and diarrhea (2.2%).
In response to a question, Dr. Neuhaus said none of the patients received postoperative radiation, as this treatment is not used in Europe for pancreatic cancer.
Dr. Neuhaus disclosed research funding and other remuneration from Lilly Oncology.
Eileen M. O'Reilly, M.D., called the results “impressive and provocative” in a discussion of the trial. She emphasized that the findings were preliminary, however, and many questions still need to be answered, including how the investigators defined disease-free survival.
As for changing the standard of practice, Dr. O'Reilly of Memorial Sloan-Kettering Cancer Center in New York said, “There is really no globally accepted standard of care for adjuvant treatment of pancreatic cancer. Observation for patients who are fit post op is probably no longer an acceptable standard, though this is controversial.”
Erlotinib + Gemcitabine = Controversy
Adding the targeted therapy erlotinib (Tarceva) to gemcitabine produced a median survival benefit of less than 1 month for patients with inoperable pancreatic cancer in another trial reported at the meeting.
The study's outcomes were statistically significant, but controversial. Investigator Malcolm J. Moore, M.D., and discussant James L. Abbruzzese, M.D., interpreted the clinical implications in a plenary session.
Patients were enrolled from October 2001 to January 2003 at 140 centers in 17 countries for this National Cancer Institute of Canada trial. Erlotinib was added to gemcitabine because it inhibits the human epidermal growth factor receptor (EGFR), which is overexpressed in pancreatic cancer.
Dr. Moore of Princess Margaret Hospital in Toronto said the trial was the first to show that an EGFR inhibitor can benefit patients with pancreatic cancer. He reported that 285 patients given gemcitabine and erlotinib had a 1-year survival rate of 24% and lived a median of 6.37 months. In contrast, for 284 patients given gemcitabine and placebo, the 1-year survival rate was 17%, with a median survival of 5.91 months.
The combination arm also had better progression-free survival: 3.75 months, compared with 3.55 months for patients who received the placebo. More of the patients given both agents had a tumor response as well: 57.5%, compared with 49.2% of the control group.