Continuing pemetrexed (Alimta) as maintenance therapy after its use as part of a 2-drug, 4-cycle induction regimen improves progression-free survival (PFS) in patients with advanced nonsquamous non–small-cell lung cancer (NSCLC).
Data from the phase 3 PARAMOUNT study, the first large trial to demonstrate the efficacy of longer-term maintenance therapy in advanced NSCLC, were presented by Luis Paz-Ares, MD, PhD, Chair of Oncology, Seville University Hospital, Spain.
Most patients with advanced NSCLC initially receive 4 cycles of cisplatin (Platinol) and pemetrexed; treatment is then stopped until the disease recurs, when a second-line therapy is administered.
Pemetrexed has demonstrated efficacy in combination with cisplatin as a first-line doublet and as a maintenance agent after therapy with a nonpemetrexed platinum doublet (“switch” maintenance).
The results of PARAMOUNT “suggest that patients can still continue to benefit from the use of the same drug rather than ‘use up’ an alternative early in the course of treatment,” Dr Paz-Ares said. “This could change the standard of care for these patients, at least in terms of maintenance treatment.”
The 939 patients with advanced nonsquamous NSCLC received the standard 4 courses of first-line induction therapy with pemetrexed and cisplatin. The 539 patients whose disease had stabilized were then randomized to maintenance pemetrexed and best supportive care or to placebo and best supportive care. Approximately 90% of patients in each group had stage IV disease.
Maintenance pemetrexed therapy showed a 38% reduction in disease progression risk, with 4.1-month PFS in the pemetrexed group compared with 2.8 months in the placebo group.
The PFS results were consistent across all subgroups analyzed. The median independently reviewed PFS (N = 472; 297 events), measured from randomization, was 3.9 months in the pemetrexed arm and 2.6 months in the placebo arm. The disease control rate was 71.8% in the pemetrexed arm and 59.6% in the placebo arm.
In commenting on the trial, Martin J. Edelman, MD, Director of Solid Tumor Oncology, University of Maryland Greenebaum Cancer Center, Baltimore, cautioned that PFS “does not necessarily predict for overall survival (OS),” as other studies have demonstrated.
ALK Inhibitors Prolong Survival
An investigational drug in a class known as anaplastic lymphoma kinase (ALK) inhibitors appears to double survival in patients with advanced NSCLC who have a certain genetic variant, said the lead investigator of an early-phase study, Alice T. Shaw, MD, PhD, a thoracic oncologist at Massachusetts General Hospital Cancer Center, Boston.
The drug, crizotinib, is an oral inhibitor of ALK and MET tyrosine kinases and their oncogenic variants; it targets tumors that have a rearrangement of the ALK gene. Approximately 4% of patients with NSCLC have tumors with ALK gene rearrangements, which stimulate the growth and survival of the tumors.
In this study, 82 patients with NSCLC who had the ALK fusion gene and whose tumors progressed despite receiving a median of 2 chemotherapy regimens received crizotinib 250 mg twice daily. There was no comparison group; instead, survival was compared with that of crizotinib-naïve controls with the ALK gene rearrangement and with patients with NSCLC without the ALK gene rearrangement.
The objective response rate was 57%, and the disease control rate was 87%. More than 90% of the patients’ tumors regressed.
Of the 82 patients enrolled in the study, 75% were alive after 1 year and 54% after 2 years. Median OS has not yet been reached, because >50% of the patients enrolled are still alive.
By comparison, among ALK-positive controls who received standard chemotherapy for NSCLC, 1-year survival is 44% and 2-year survival is only 12%, said Dr Shaw. Median OS in this group is 6 months.
Median OS among patients with NSCLC without the ALK rearrangement is not significantly different from those with the ALK rearrangement. The median OS in the patients who received crizotinib in this study, compared with that in the historical controls (crizotinib-naïve patients who lack the ALK rearrangement or the epidermal growth factor receptor genetic mutation), was significantly improved in those with the ALK rearrangement.