The Journal Watch selects JAMA paper with 4Pharma data analyses to the top 10 stories in oncology/hematology published in 2012

John Gymer (john.gymer a, Feb 5th 2013

Joensuu H, Eriksson M, Sundby Hall K, Hartmann JT, Pink D, Schütte J, Ramadori G, Hohenberger P, Duyster J, Al-Batran SE, Schlemmer M, Bauer S, Wardelmann E, Sarlomo-Rikala M, Nilsson B, Sihto H, Monge OR, Bono P, Kallio R, Vehtari A, Leinonen M, Alvegård T, Reichardt P.
JAMA. 2012 Mar 28;307(12):1265-72. doi: 10.1001/jama.2012.347

Treatment for patients with gastrointestinal stromal tumors (GISTs) was revolutionized with the advent of imatinib, which targets mutated KIT and PDGFR gene products that drive growth in these rare cancers. Imatinib results in dramatic tumor response and protracted survival in patients with metastatic disease, and administration of adjuvant imatinib for 12 months after resection prolongs recurrence-free survival (RFS) compared with surgery alone. However, recurrence is common after discontinuation of adjuvant treatment.

To determine whether extending adjuvant imatinib treatment would benefit patients at high risk for GIST recurrence after surgery, investigators conducted an international, multicenter, phase III trial comparing 12 months versus 36 months of imatinib (400 mg daily) after resection of high-risk GIST, defined as a tumor diameter >10 cm, >10 mitoses per high power field, tumor diameter >5 cm and mitotic count >5, or tumor rupture before or during surgery. Of 400 patients, 81% to 85% underwent R0 resection, 41% to 46% had tumors 5 cm to 10 cm in size, and 91% had documented mutations in KIT or PDGFRA.

The 5-year recurrence-free survival rate was higher with 36 months versus 12 months of imatinib treatment (65.6% vs. 47.9%; hazard ratio, 0.46; P<0.001), as was the 5-year overall survival rate (92.0% vs. 81.7%; HR 0.45; P=0.02). More patients in the 36-month group than the 12-month group experienced grade 3 and 4 adverse events (32.8% vs. 20.1%) and discontinued therapy for reasons other than disease progression (25.8% vs. 12.6%).

This landmark trial indicates that a strategy of extending imatinib adjuvant therapy to 3 years improves recurrence free and overall survival and establishes a new standard of care. The question now is whether imatinib should be extended for even longer periods after surgery for high-risk disease or continued indefinitely.