SOLID TUMORS
Clinical Oncology News • July 2011
GIST Three years of imatinib One year of imatinib
THREE YEARS Hospital in Helsinki, at the recent American Society of Clinical Oncology (ASCO) annual meeting (abstract LBA1). Previous trials have shown that one year of adjuvant imatinib reduces the risk of GIST recurrence compared with placebo but have not yet demonstrated an improvement in survival. Approximately 85% of patients who have advanced GIST respond to imatinib, with partial remission or stable disease lasting a median of two years. High-risk GISTs, which are defined by clinical factors including size (>5 cm), high cell proliferation rate and/ or location, are associated with at least a 50% five-year risk for recurrence after surgery, said Dr. Joensuu. At the ASCO meeting, Dr. Joensuu presented results from a prospective, openlabel, randomized Phase III study carried out in Finland, Germany, Norway and Sweden. The study randomly assigned 400 high-risk GIST patients to one year of imatinib (200 patients, median age 62 years) or three years of imatinib (200 patients, median age 60 years). All patients received imatinib 400 mg daily. After a median follow-up of 54 months in the intention-to-treat population, the results showed a significantly higher five-year recurrence-free survival in patients treated for three years compared with one year (65.6% vs. 47.9%; P<0.0001) (Figure 1). Similarly, the five-year overall survival rate was significantly higher for patients receiving imatinib for three years (92% vs. 81.7%; P=0.019) (Figure 2). “The longer treatment prevented recurrence of GIST in 54% of patients, and there were 55% fewer deaths in the
Recurrence-free Survival Rate, %
continued from page 1
100 80 65.6
60 47.9
40 20 0
Figure 1. Five-year recurrence-free survival in GIST.
Three years of imatinib One year of imatinib
100
Overall Survival Rate, %
10
80
92 81.7
60 40 20 0
Figure 2. Five-year overall survival in GIST.
three-year versus the one-year group,” Dr. Joensuu said. “Historically, 50% of GIST patients had died within five years. With imatinib, we are making substantial improvements.” The treatment was well tolerated, with the most frequent side effects including anemia, eyelid swelling, fatigue, nausea and muscle cramps, which were usually
mild. There were slightly more treatment discontinuations due to adverse events in the three-year group (14% vs. 8%) and slightly more grade 3/4 adverse events in the three-year group (33% vs. 20%). As in previous studies, few patients developed resistance to adjuvant imatinib. Only 2% of patients in the one-year group and 6.1% of those in the three-year group stopped treatment because of GIST recurrence while receiving imatinib. “Compared to one year of adjuvant imatinib, three years of imatinib improves recurrence-free survival and overall survival as treatment of GIST patients who have a high estimated risk for recurrence after surgery,” Dr. Joensuu said. He noted that there are no data that these patients might survive longer if they received five years of adjuvant imatinib, but that studies analyzing GIST risk factors and addressing longer treatment times with adjuvant imatinib are currently under way. Clinicians need to follow these patients carefully to detect early recurrence, he said. “There is evidence that patients with small tumors will respond longer to imatinib than patients with bulky tumors,” said Dr. Joensuu. “If we can detect the tumor when tumor volume is small, there is less likelihood the patient will develop resistance to imatinib.” Charles Blanke, MD, chief of medical oncology at University of British Columbia, Vancouver, was asked to discuss the study at ASCO. “Three years of postoperative imatinib treatment represent the new gold standard for patients with resected, high-risk GIST,” Dr. Blanke said. “The overall survival advantage demonstrated means we cannot try to ‘catch up’ later in the advanced disease setting.” Dr. Blanke pointed out that imatinib is not a cure for advanced GIST. “Even patients in complete remission at five
Endoscopic image of GIST in fundus of stomach, seen on retroflexion.
years are not cured and need to stay on imatinib,” he said. “We also still don’t know how long to administer imatinib for GIST in the postoperative setting.” Dr. Blanke asked, “Should we treat longer than three years? Should we treat forever? There are many reasons to think that giving imatinib for a longer period would be better. For now, if I were a patient with resected GIST, I would request more. As a compliant oncologist, I personally will offer imatinib indefinitely. I reserve the right to change my mind, pending the longer-term overall survival results from SSG [Scandinavian Sarcoma Group] XVIII and the findings from the recently completed PERSIST-5 trial. But I don’t think GISTs are curable (with imatinib) even in the adjuvant setting.” At the moment, Dr. Blanke said, “Given the possibility that we need to treat for a very long term, coupled with the difficulty in patients taking long durations of the drug, I will recommend adjuvant imatinib to patients who have a 50% chance of recurrence following surgery.” He believes the number used to predict recurrence and then treat will be lower in the community. Drs. Joensuu and Blanke disclosed that they serve in a consultant or advisory role for Novartis. Dr. Joensuu has also received honoraria from the company. —Mark Furst
FDA NEWS continued from page 5
had undergone stem cell transplant. All patients were evaluated for toxicity; two patients discovered to be ineligible were excluded from response assessment. Common AEs were nausea, fatigue, and transient thrombocytopenia and granulocytopenia. CRs were observed in eight and PRs in nine of 45 patients, for an ORR of 38%. The median duration of overall response was 8.9 months (range, two to 74). Responses were observed in various subtypes, with six responses among the 18 patients with prior stem cell transplant. Romidepsin also is approved for the treatment of cutaneous T-cell lymphoma in patients who have received at least one prior systemic therapy.
New Formulation of Lupron Depot
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he FDA has approved a new 45-mg six-month administration formulation of leuprolide acetate
for depot suspension (Lupron Depot, Abbott), an injectable medication used for the palliative treatment of advanced prostate cancer. The three current formulations of Lupron Depot have allowed patients to receive treatment every one, three or four months. The newly approved sixmonth formulation will provide additional dosing flexibility for patients with advanced prostate cancer. Approval was supported by a 48-week, open-label study involving 151 patients with prostate cancer. Patients received two injections, 24 weeks apart, and were followed for nearly 12 months to evaluate testosterone suppression and safety. Overall, testosterone suppression with the new 45-mg six-month formulation was sustained in patients throughout the treatment period. The onset of testosterone suppression was consistent with other currently available formulations of the drug. The most common side
effects were flushing, injection site pain, respiratory infection and fatigue.
FDA Clears New PET/MRI Scanning System
Clearance was based on bench tests that compared the device with a predicate PET/CT device. The Biograph mMR system is indicated for a patient who needs diagnostic PET or MRI imaging. People with pacemakers, defibrillators or other implanted electronic devices, however, should not be scanned with the Biograph mMR system unless those devices are specifically indicated for use in the MRI environment.
FDA Clears New HER2 Test
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T
he FDA has cleared the Siemens Biograph mMR system, the first device to simultaneously perform a positron emission tomography (PET) scan and a magnetic resonance imaging (MRI) scan. The system reduces radiation dose and increases soft tissue contrast.
he FDA has approved a new test to determine HER2 positivity. Inform Dual ISH (Ventana Medical Systems) allows laboratory personnel, using a stain, to count the number of copies of HER2 genes on chromosome 17 in a small sample of the breast tumor. Copies of the HER2 gene appear black and copies of chromosome 17 appear red, and these changes can be seen with see FDA NEWS, page 14