ALIMTA-AVASTIN MAINTENANCE IN NSCLC

An induction and maintenance regimen based on pemetrexed (Alimta) slightly delayed progression in late-stage nonsquamous non-small cell lung cancer (NSCLC) but had no impact on overall survival compared with a paclitaxel-based regimen, a trial showed.

Progression-free survival came out at a median of 6 months for pemetrexed, carboplatin (Paraplatin), and bevacizumab (Avastin) followed by pemetrexed plus bevacizumab compared with 5.6 months on paclitaxel, carboplatin, and bevacizumab then bevacizumab alone (P=0.012), Jyoti D. Patel, MD, of Northwestern University in Chicago, and colleagues found.

For the primary endpoint of overall survival (OS), though, the hazard ratio indicated no difference between the two regimens (P=0.949), the group reported online in the Journal of Clinical Oncology.

While the trial was powered for superiority rather than equivalence, the efficacy results fit with those of other phase III first-line trials of platinum doublet induction followed by continued maintenance for patients who do not progress, they noted.

"The similar efficacy seen in this study between treatment arms and compared with other platinum doublet therapy allows clinicians to choose a therapy most appropriate for a given patient on the basis of that specific patient's clinical situation and tolerance to toxicities," Patel's group concluded.

The ATLAS trial reported earlier this month that maintenance therapy with erlotinib (Tarceva) added to bevacizumab modestly delayed progression but not death in advanced NSCLC after chemotherapy with bevacizumab.

But the AVAPERL trial had shown that adding pemetrexed to bevacizumab for maintenance therapy was better than bevacizumab alone after induction chemotherapy.

Guidelines recommend four to six cycles of platinum-based induction therapy for advancedNSCLC patients with good performance status, with either a platinum doublet plus bevacizumab or a platinum drug with pemetrexed as options for nonsquamous cases.

The phase III PointBreak trial included 439 patients with previously untreated stage IIIB or IV nonsquamous NSCLC and good performance status.

They were randomized to pemetrexed (500 mg/m²) or paclitaxel (200 mg/m²) along with with carboplatin (area under the curve 6) and bevacizumab (15 mg/kg) every 3 weeks for up to four cycles.

For maintenance, those on pemetrexed continued it with bevacizumab at the same doses, while the other group got bevacizumab alone.

Median OS was 12.6 months with the pemetrexed-based regimen and 13.4 months with the paclitaxel-based regimen, for an HR of 1.00 (95% CI 0.86-1.16).

Survival rates at 12 months were 52.7% versus 54.1%, respectively, and 24.4% versus 21.2% at 24 months.

"The two Kaplan-Meier overall survival curves are superimposable," the researchers noted.

Overall response rates were 34.1% with the pemetrexed regimen and 33% in the paclitaxel group. Disease control rates were 65.9% and 69.8%, respectively.

"Although the toxicity profiles for the regimens differed, both demonstrated tolerability," Patel's group wrote.

The pemetrexed group had significantly more study drug-related grade 3 or 4 anemia (14.5% versus 2.7%), thrombocytopenia (23.3% versus 5.6%), and fatigue (10.9% versus 5%).

The paclitaxel group had significantly more grade 3 or 4 neutropenia (40.6% versus 25.8%), febrile neutropenia (4.1% versus 1.4%), sensory neuropathy (4.1% versus 0%), and alopecia (grade 1 or 2 36.8% versus 6.6%).

Deaths and their causes (hemorrhage, cardiac disorders, and infection) were similar between groups. Only 2% of deaths in the safety population were drug related, the authors reported.

Study limitations included inability to separate the effects of induction and maintenance on the outcomes and limited comparability with other trials, which have randomized post-induction therapy.