Study finds no benefit from lapatinib for HER2-positive gastric cancer patients

Addition of the anti-HER2 antibody lapatinib to capecitabine and oxaliplatin (CapeOx) as first-line treatment for advanced gastroesophageal adenocarcinoma did not significantly improve overall survival (OS) in the total study population, but subgroup analysis showed benefits for patients from Asia and those younger than 60 years.

The primary endpoint, median OS, was similar in the lapatinib and placebo arms at 12.2 months and 10.5 months (hazard ratio, 0.91; 95% confidence interval, 0.73-1.12; P = .35). Median PFS was significantly improved in the lapatinib arm, compared with placebo at 6.0 months vs. 5.4 months (HR, 0.82; 95% CI, 0.68-1.00; P = .04).

Preplanned exploratory analysis of OS by geographic location showed that patients from Asia had significantly improved OS with lapatinib: 16. 5 months vs. 10.9 months (HR, 0.68; 95% CI, 0.48-0.96; P = .03). Patients younger than 60 years also benefited, with median OS of 12.9 months vs. 9.0 months for lapatinib and placebo arms, respectively (HR, 0.69; 95% CI, 0.51-0.94; P = .01)

Patients in the lapatinib arm experienced a slightly higher incidence of adverse events (94% vs. 88%), with the most common events in both arms being diarrhea, nausea, vomiting, and decreased appetite.

“The use of lapatinib in combination with CapeOx in patients with HER2-positive gastric cancer cannot be recommended. Future research may identify a subgroup of patients who benefit from such treatment, although there are several new anti-HER2 agents, such as pertuzumab and ado-trastuzumab, that are being tested in HER2-positive gastric cancer,” wrote Dr. J. Randolph Hecht, professor of clinical medicine in the University of California, Los Angeles, and director of the UCLA Gastrointestinal Oncology Program (J Clin Oncol. 2015 Dec 2. doi: 10.1200/JCO.2015.62.6598).

The randomized phase III TRIO-013/LOGiC trial evaluated 545 patients with unresectable adenocarcinoma of the stomach, esophagus, or gastroesophageal junction with confirmed HER2 amplification.

Given that anti-HER2 antibodies (lapatinib- and trastuzumab-based regimens) have improved outcomes in patients with HER2-positive breast cancer, and trastuzumab plus cisplatin-based therapy significantly improved OS among of patients with HER2-positive gastric cancer in the ToGA trial, the researchers offered several explanations for the nonsignificant improvement reported here. The toxicity profiles differ between lapatinib and trastuzumab, particularly with regard to diarrhea, which may affect patients with gastroesophageal cancer more than other populations. There are concerns about absorption with the use of oral agents, especially among the 23% of patients in the study who had their pylorus removed.

GlaxoSmithKline, in collaboration with Translational Research in Oncology (TRIO), funded the work. Dr. Hecht disclosed ties with Amgen, Roche/Genentech, Pfizer, Immunomedics, Gilead Sciences, Celgene, and OncoMed. Several of his coauthors reported ties to industry.

Addition of the anti-HER2 antibody lapatinib to capecitabine and oxaliplatin (CapeOx) as first-line treatment for advanced gastroesophageal adenocarcinoma did not significantly improve overall survival (OS) in the total study population, but subgroup analysis showed benefits for patients from Asia and those younger than 60 years.

The primary endpoint, median OS, was similar in the lapatinib and placebo arms at 12.2 months and 10.5 months (hazard ratio, 0.91; 95% confidence interval, 0.73-1.12; P = .35). Median PFS was significantly improved in the lapatinib arm, compared with placebo at 6.0 months vs. 5.4 months (HR, 0.82; 95% CI, 0.68-1.00; P = .04).

Preplanned exploratory analysis of OS by geographic location showed that patients from Asia had significantly improved OS with lapatinib: 16. 5 months vs. 10.9 months (HR, 0.68; 95% CI, 0.48-0.96; P = .03). Patients younger than 60 years also benefited, with median OS of 12.9 months vs. 9.0 months for lapatinib and placebo arms, respectively (HR, 0.69; 95% CI, 0.51-0.94; P = .01)

Patients in the lapatinib arm experienced a slightly higher incidence of adverse events (94% vs. 88%), with the most common events in both arms being diarrhea, nausea, vomiting, and decreased appetite.

“The use of lapatinib in combination with CapeOx in patients with HER2-positive gastric cancer cannot be recommended. Future research may identify a subgroup of patients who benefit from such treatment, although there are several new anti-HER2 agents, such as pertuzumab and ado-trastuzumab, that are being tested in HER2-positive gastric cancer,” wrote Dr. J. Randolph Hecht, professor of clinical medicine in the University of California, Los Angeles, and director of the UCLA Gastrointestinal Oncology Program (J Clin Oncol. 2015 Dec 2. doi: 10.1200/JCO.2015.62.6598).

The randomized phase III TRIO-013/LOGiC trial evaluated 545 patients with unresectable adenocarcinoma of the stomach, esophagus, or gastroesophageal junction with confirmed HER2 amplification.

Given that anti-HER2 antibodies (lapatinib- and trastuzumab-based regimens) have improved outcomes in patients with HER2-positive breast cancer, and trastuzumab plus cisplatin-based therapy significantly improved OS among of patients with HER2-positive gastric cancer in the ToGA trial, the researchers offered several explanations for the nonsignificant improvement reported here. The toxicity profiles differ between lapatinib and trastuzumab, particularly with regard to diarrhea, which may affect patients with gastroesophageal cancer more than other populations. There are concerns about absorption with the use of oral agents, especially among the 23% of patients in the study who had their pylorus removed.

GlaxoSmithKline, in collaboration with Translational Research in Oncology (TRIO), funded the work. Dr. Hecht disclosed ties with Amgen, Roche/Genentech, Pfizer, Immunomedics, Gilead Sciences, Celgene, and OncoMed. Several of his coauthors reported ties to industry.

Addition of the anti-HER2 antibody lapatinib to capecitabine and oxaliplatin (CapeOx) as first-line treatment for advanced gastroesophageal adenocarcinoma did not significantly improve overall survival (OS) in the total study population, but subgroup analysis showed benefits for patients from Asia and those younger than 60 years.

The primary endpoint, median OS, was similar in the lapatinib and placebo arms at 12.2 months and 10.5 months (hazard ratio, 0.91; 95% confidence interval, 0.73-1.12; P = .35). Median PFS was significantly improved in the lapatinib arm, compared with placebo at 6.0 months vs. 5.4 months (HR, 0.82; 95% CI, 0.68-1.00; P = .04).

Preplanned exploratory analysis of OS by geographic location showed that patients from Asia had significantly improved OS with lapatinib: 16. 5 months vs. 10.9 months (HR, 0.68; 95% CI, 0.48-0.96; P = .03). Patients younger than 60 years also benefited, with median OS of 12.9 months vs. 9.0 months for lapatinib and placebo arms, respectively (HR, 0.69; 95% CI, 0.51-0.94; P = .01)

Patients in the lapatinib arm experienced a slightly higher incidence of adverse events (94% vs. 88%), with the most common events in both arms being diarrhea, nausea, vomiting, and decreased appetite.

“The use of lapatinib in combination with CapeOx in patients with HER2-positive gastric cancer cannot be recommended. Future research may identify a subgroup of patients who benefit from such treatment, although there are several new anti-HER2 agents, such as pertuzumab and ado-trastuzumab, that are being tested in HER2-positive gastric cancer,” wrote Dr. J. Randolph Hecht, professor of clinical medicine in the University of California, Los Angeles, and director of the UCLA Gastrointestinal Oncology Program (J Clin Oncol. 2015 Dec 2. doi: 10.1200/JCO.2015.62.6598).

The randomized phase III TRIO-013/LOGiC trial evaluated 545 patients with unresectable adenocarcinoma of the stomach, esophagus, or gastroesophageal junction with confirmed HER2 amplification.

Given that anti-HER2 antibodies (lapatinib- and trastuzumab-based regimens) have improved outcomes in patients with HER2-positive breast cancer, and trastuzumab plus cisplatin-based therapy significantly improved OS among of patients with HER2-positive gastric cancer in the ToGA trial, the researchers offered several explanations for the nonsignificant improvement reported here. The toxicity profiles differ between lapatinib and trastuzumab, particularly with regard to diarrhea, which may affect patients with gastroesophageal cancer more than other populations. There are concerns about absorption with the use of oral agents, especially among the 23% of patients in the study who had their pylorus removed.

GlaxoSmithKline, in collaboration with Translational Research in Oncology (TRIO), funded the work. Dr. Hecht disclosed ties with Amgen, Roche/Genentech, Pfizer, Immunomedics, Gilead Sciences, Celgene, and OncoMed. Several of his coauthors reported ties to industry.