An experimental first-line chemotherapy regimen that included pemetrexed did not improve overall survival compared with standard paclitaxel-based treatment in a phase III randomized, open-label study of more than 900 patients with late-stage lung cancer.
The experimental regimen did improve progression-free survival, a secondary end point of the study called POINTBREAK by Eli Lilly.
"The fact that there was no improvement in survival with the experimental regimen was disappointing, but these findings are important as we continue to navigate ways to improve survival for this devastating disease," lead author Dr. Jyoti D. Patel said during a press briefing at the Chicago Multidisciplinary Symposium in Thoracic Oncology.
Funded by Lilly, the phase III study compared an experimental regimen of pemetrexed (Alimta) plus carboplatin plus bevacizumab (Avastin) followed by maintenance pemetrexed plus bevacizumab (the Pem arm) with a Food and Drug Administration–approved regimen of paclitaxel plus carboplatin plus bevacizumab followed by maintenance bevacizumab (the Pac Arm) in previously untreated patients with stage IIIB or IV nonsquamous non–small cell lung cancer (NS-NSCLC).
A total of 939 such patients who had Eastern Oncology Cooperative Group performance status of 0-1 were randomized. Patients in the experimental arm received pemetrexed (500 mg/m2) plus carboplatin (AUC = 6) plus bevacizumab (15 mg/kg) along with folic acid, vitamin B12 and dexamethasone supplementation. The control group received paclitaxel (200 mg/m2) plus carboplatin (AUC = 6) plus bevacizumab (15 mg/kg), and dexamethasone, diphenhydramine, and cimetidine or ranitidine premedications.
Both regimens were given every 3 weeks for up to four cycles. Patients who continued without progressive disease received maintenance pemetrexed plus bevacizumab (Pem Arm) or maintenance bevacizumab (Pac Arm).
The overall patient population had a median age of 64.7 years, was 53.2% male, and 85.7% white. Nearly all, 90.0%, had stage IV NSCLC, and 79.2% had adenocarcinoma. Only 11.6% had never smoked.
Median overall survival – the primary end point – was 12.6 months in the experimental group (Pem arm) and 13.4 months for the control group (Pac arm), a nonsignificant difference (hazard ratio, 1.00; P = .949. The 1-year survival rates were 52.7% and 54.1%, respectively; the 2-year rates were 24.4% and 21.2%, respectively.
Median progression-free survival was significantly longer for the Pem arm: 6.0 versus 5.6 months (HR, 0.83; P = .012. The overall response rates were 34.1% with pemetrexed and 33.0% with paclitaxel; the disease control rates were 65.9% and 69.8%, respectively, Dr. Patel reported.
The pemetrexed arm has significantly more study drug-related grade 3/4 anemia (14.5% vs. 2.7%), thrombocytopenia (23.3% vs. 5.6%) and fatigue (10.9% vs. 5.0%). The paclitaxel arm had significantly more grade 3/4 neutropenia (40.6% vs. 25.8%), febrile neutropenia (4.1% vs. 1.4%), sensory neuropathy (4.1% vs. 0) and complete (grade 2) alopecia (21.4 % vs. 1.1%). These event rates are similar to those seen in previous trials, she noted.
Hemorrhage – either gastrointestinal or pulmonary and thromboembolic events were infrequent and similar between arms. There were very few grade 5 events, she said.
Study drug-related discontinuations due to severe adverse events (2.7% vs. 3.6%), adverse events (10.4% vs. 9.0%), and study drug-related deaths due to adverse events (1.8% vs. 2.3%) were similar between the two groups (Pem arm vs. Pac arm, respectively).
"It is important to note that both regimens demonstrated tolerability, although their toxicities differed. These differences can be important for our patients," said Dr. Patel of the department of medicine-hematology/oncology at Northwestern University, Chicago.
The Chicago Multidisciplinary Symposium in Thoracic Oncology is sponsored by the American Society of Clinical Oncology, the American Society for Radiation Oncology, the International Association for the Study of Lung Cancer, and the University of Chicago
Dr. Patel received a research grant from Eli Lilly for this study. Several of her coauthors had ties to Lilly and other companies including Genentech, Pfizer, and GlaxoSmithKline.