Loading...
Recent studies have shown that front-line therapy with inhibitors of epidermal growth factor receptor (EGFR) tyrosine kinase (TK) is more effective than cytotoxic chemotherapy at improving progression-free survival (PFS) in patients with metastatic non–small-cell lung cancer (NSCLC) and EGFR mutations.
Now, Yang and colleagues report results of the randomized, phase III LUX-Lung 3 trial [Abstract LBA7500] of the irreversible EGFR TK inhibitor afatinib versus cisplatin plus pemetrexed as first-line treatment for 345 patients with advanced adenocarcinoma of the lung harboring EGFR-activating mutations. Testing for EGFR mutations in tumor specimens was conducted by a central laboratory using the TheraScreen polymerase chain reaction assay.
Median PFS (the primary endpoint) was longer with afatinib than with cisplatin plus pemetrexed (11.1 months vs. 6.9 months; hazard ratio, 0.58; P=0.0004). For patients with the more common mutation (exon 19 deletion and L858R), median PFS was even longer with afatinib than with cisplatin and pemetrexed (13.6 months vs. 6.9 months; HR, 0.47; P<0.0001). Adverse effects in both treatment arms were consistent with known toxicities of EGFR TK inhibitors and chemotherapy. However, grade 3 diarrhea was reported in 14% of patients on the afatinib arm compared with 0% in the chemotherapy arm.
These findings reinforce previous observations that EGFR TK inhibitors significantly improve PFS over cytotoxic chemotherapy in the front-line therapy of patients with EGFR-mutant NSCLC. Afatinib also shows some activity in patients who harbor T790M mutations in the EGFR TK domain, a subgroup that is notoriously resistant to reversible EGFR TK inhibitors such as gefitinib and erlotinib. However, it is unclear if afatinib would be more effective than erlotinib or gefitinib in patients with known EGFR TK mutations.
In a prior report of the randomized, phase III PARAMOUNT trial (JW Oncol Hematol July 12 2011), 539 patients with locally advanced nonsquamous NSCLC who experienced no progressive disease after four cycles of pemetrexed and cisplatin therapy were randomized 2:1 to receive pemetrexed continuation maintenance or placebo. Median PFS (the primary endpoint) was longer with pemetrexed maintenance than with placebo.
Paz-Ares and colleagues now report overall survival (OS) results, the secondary endpoint, from the PARAMOUNT trial [Abstract LBA7507]. As with median PFS, median OS was longer with maintenance pemetrexed than with placebo (13.9 months vs. 11 months; HR, 0.78; P=0.0195). Although maintenance pemetrexed was tolerated well, fatigue, anemia, and neutropenia were more common with pemetrexed than with placebo.
These results provide the first direct evidence that continuation maintenance therapy improves OS in patients with nonsquamous NSCLC. Maintenance therapy with pemetrexed for the select group of patients who have excellent performance status and no evidence of progressive disease after four cycles of platinum-based therapy is a reasonable option.
Fluorodeoxyglucose (FDG) positron emission tomography (PET) is commonly used in the diagnosis and staging of patients with suspected or confirmed NSCLC. A prior meta-analysis (JAMA 2001; 285:914) reported a sensitivity of 94% and specificity of 83%, although it is not clear how accurate FDG-PET is in the areas of the U.S. with endemic fungal lung disease.
Grogan and colleagues presented the results of the ACOSOG Z4031 trial [Abstract 7008], which assessed the diagnostic accuracy of FDG-PET in patients who had clinical stage I confirmed or suspected NSCLC and underwent surgical resection.
Using case forms and reports of standardized uptake values of FDG-PET scans from 51 sites in 39 U.S. cities, the investigators found that in 682 patients with preoperative FDG-PET results, 82% of cancerous lesions and, remarkably, 69% of benign lesions were FDG avid. The accuracy of FDG-PET in diagnosing lung cancer was 73%, with a sensitivity of 82% and a specificity of only 31%. Sensitivity differed by region; for example, sensitivity in Durham, North Carolina, was greater than in Los Angeles (91% vs. 67%; P=0.03). The accuracy of FDG-PET improved with the size of the lesion: less than 50% accuracy with lesions less than 2 cm, and 80% accuracy with lesions greater than 30 cm. Granulomas, which can occur with fungal lung disease, accounted for the majority (69%) of false-positive FDG-PET scans
FDG-PET performed poorly in this study compared with recent studies. Results of FDG-PET scans should be interpreted with caution, particularly in patients with small lesions and in geographic regions where fungal lung disease is endemic.