• Gastrointestinal Cancers Clinical Trials

• Gastrointestinal Cancers
• Oncology Clinical Trials
• Oncology

The addition of lapatinib (L) to capecitabine plus oxaliplatin (Cape/Ox) does not improve overall survival (OS) in patients with locally advanced or metastatic gastric, esophageal, or gastroesophageal junction cancer whose tumors have amplification of the HER2 gene, although an improvement in survival was seen in patients of Asian descent and those aged <60 years.

Results were presented from the Lapatinib Optimization Study in ErbB2 (HER2) Positive Gastric Cancer [LOGiC; NCT00680901; J Clin Oncol 2013 (suppl; abstr LBA4001)] by J. Randolph Hecht, MD, University of California, Los Angeles, Los Angeles, California, USA, which compared Cape/Ox alone or in combination with lapatinib (Cape/Ox/L) as first-line treatment for patients with advanced or metastatic HER2-positive upper gastrointestinal tract cancers.

The Phase 3 trial included 545 patients enrolled between June 2008 and January 2012 from 186 centers in 22 countries. Eligible patients included those with locally advanced or metastatic histologically confirmed adenocarcinoma of the stomach, esophagus, or gastroesophageal junction; measurable or evaluable disease according to RECIST; HER2-positive disease, ≥18 years of age; ECOG PS <2, and no prior palliative chemotherapy.

HER2-positive disease was confirmed in a central laboratory in 487 of the 545 patients by fluorescence in situ hybridization. These patients were used as the primary efficacy population (PEP) to evaluate the primary outcome of OS.

Of these 487 patients, 249 were randomized to Cape/Ox/L (oxaliplatin 130 mg/m² Day 1, capecitabine 850 mg/m² BID Days 1 to 14, and lapatinib 1250 mg QD Days 1 to 21) and 238 to Cape/Ox plus placebo (Cape/Ox/P).

Based on this PEP, the study found no difference in OS between the two treatments with a median OS of 12.2 months and 10.5 months for Cape/Ox/L and Cape/Ox/P, respectively (HR, 0.91; 95% CI, 0.73 to 1.12; p=0.3492).

Under prespecified subgroup analyses, however, significant improvements in OS were seen in Asian patients compared with populations in the rest of the world (ROW) and those aged <60 years. Asian patients had an improvement in median OS from 10.9 months with Cape/Ox/P to 16.5 months with Cape/Ox/L (HR, 0.68; 95% CI, 0.48 to 0.96). The median OS in ROW populations improved from 9.1 for Cape/Ox/P to 10.0 months for Cape/Ox/L (HR, 1.04; 95% CI, 0.79 to 1.37).

Patients aged <60 years also had significantly improved OS compared with those aged ≥60 years, with an improvement in median OS from 9.0 months with Cape/Ox/P to 12.9 months with Cape/Ox/L (HR, 0.69; 95% CI, 0.51 to 0.94). In patients aged ≥60 years, the median OS was 10.9 months with Cape/Ox/P and 11.3 months with Cape/Ox/L (HR, 1.08; 95% CI, 0.81 to 1.45).

Secondary outcomes of the study showed a progression-free survival of 6 months and 5.4 months for Cape/Ox/L and Cape/Ox/P, respectively, as well as overall response rates of 53% and 40%, respectively, with a median duration of response of 7.3 months and 5.6 months, respectively.

Toxicity was comparable between the two treatment arms, except that Cape/Ox/L was associated with increased overall diarrhea (58%) compared with Cape/Ox/P (29%), Grade 3 diarrhea (12% vs 3%), and skin rash (21% vs 7%).

Based on these results, no improvement in OS was seen with the addition of lapatinib to Cape/Ox except for in Asian patients and those aged <60 years; however, the addition of lapatinib did confer some improvement in progression-free survival and overall response rates.

• © 2013 MD Conference Express®