INDIANAPOLIS, -- Eli Lilly and Company (NYSE: LLY) announced today that the Phase III POINTBREAK trial did not meet its primary endpoint of improved overall survival for patients with nonsquamous non-small cell lung cancer (NSCLC) who were randomized to receive a combination of ALIMTA (pemetrexed for injection) with bevacizumab (AVASTIN) and carboplatin induction followed by ALIMTA plus bevacizumab maintenance–the ALIMTA arm–compared to the combination of paclitaxel with bevacizumab and carboplatin followed by bevacizumab maintenance–the paclitaxel arm.
The study did meet one of its secondary endpoints of improved progression-free survival for the ALIMTA arm. Results will be presented on September 7 at the Chicago Multidisciplinary Symposium in Thoracic Oncology.
"Phase II results with this combination were promising and we were hoping to demonstrate an improvement in survival for nonsquamous NSCLC patients, so we are disappointed with the results of this trial," said Allen S. Melemed, M.D., M.B.A., senior medical director with Lilly Oncology. "POINTBREAK did show an improvement in progression-free survival, though this did not translate to an overall survival advantage."
Patients with previously untreated stage IIIB/IV nonsquamous NSCLC and a performance status of 0-1 (n=939) were randomized to receive ALIMTA (500 mg/m2) + carboplatin (AUC 6) + bevacizumab (15 mg/kg), along with dexamethasone and folic acid and vitamin B12 supplementation (n=472) or paclitaxel (200 mg/m2) + carboplatin (AUC 6) + bevacizumab (15 mg/kg), with dexamethasone (n=467).
First-line treatments were conducted every three weeks for up to four cycles. Patients whose disease did not progress following first-line treatment received either maintenance of ALIMTA plus bevacizumab (n=292) on the ALIMTA arm, while those on the paclitaxel arm received bevacizumab as a single agent (n=298).
Overall survival for patients randomized to the ALIMTA arm achieved a median overall survival of 12.6 months versus 13.4 months for patients on the paclitaxel arm (HR 1.00; p=0.949), a result that demonstrated no statistical difference. POINTBREAK showed a statistically significant improvement in progression-free survival (6.0 months versus 5.6 months [HR 0.83; p=0.012]) in the ALIMTA arm. Secondary objectives also included overall response rate (34.1% versus 33.0%) and disease control rate (65.9% versus 69.8%), which did not show a difference between the two arms.
A pre-specified non-comparative survival analysis for a subgroup of patients treated with maintenance therapy showed a median survival of 17.7 months for the ALIMTA arm and 15.7 months for the paclitaxel arm and progression-free survival of 8.6 months and 6.9 months. Toxicity profiles differed between regimens.
Significantly (p ≤ 0.025) more drug-related grade 3/4 anemia (14.5% versus 2.7%), thrombocytopenia (23.3% versus 5.6%) and fatigue (10.9% versus 5.0%) were seen on the ALIMTA arm. Significantly more grade 3/4 neutropenia (40.6% versus 25.8%), febrile neutropenia (4.1% versus 1.4%), sensory neuropathy (4.1% versus 0%) and grade 1/2 alopecia (36.8% versus 6.6%) were seen in patients on the paclitaxel arm.
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