Targeting HER1/2 falls flat in bladder cancer trial

Patients with metastatic urothelial bladder cancer (UBC) overexpressing HER1 or HER2 did not benefit from a course of lapatinib maintenance therapy following chemotherapy, a U.K.-based research group reported.

The phase III study, led by Thomas Powles, MD, of Queen Mary University of London, randomized 232 patients (mean age 71, about 75% male) with HER1- or HER2-positive metastatic UBC who had not progressed during platinum-based chemotherapy to placebo or lapatinib (Tykerb), an oral medication that targets HER1 and HER2 and is marketed for use in some breast cancers. The lapatinib-treated group saw no significant gains in either progression-free (PFS) or overall survival (OS), Dr. Powles and associates reported (J Clin Oncol. 2016 Oct 31. doi: 10.1200/JCO.2015.66.3468).

The median PFS for patients receiving lapatinib 1,500 mg daily was 4.5 months, compared with 5.1 months for the placebo group (hazard ratio, 1.07; 95% CI, 0.81-1.43; P = .63), while OS after chemotherapy was 12.6 and 12 months, respectively (HR 0.96; 95% CI, 0.70-1.31; P = .80). A subgroup of patients strongly positive for either or both receptors did not see significant OS or PFS benefit associated with lapatinib, a finding that the investigators said reinforced a lack of benefit.

While previous studies have indicated roles for both HER1 and HER2 in bladder cancer progression, targeting them “may not be of clinical benefit in UBC,” Dr. Powles and his colleagues wrote.

Patients with metastatic UBC have short overall survival following first-line chemotherapy, and few proven second-line treatment options exist besides additional chemotherapy, whose benefit is controversial, the researchers noted.

Despite this trial’s negative result for postchemotherapy maintenance treatment with lapatinib, Dr. Powles and his colleagues said their study, which screened 446 patients with metastatic UBC before randomizing slightly more than half, nonetheless shed some light on this difficult-to-treat patient group, including identifying three prognostic factors associated with poor outcome: radiologic progression during chemotherapy, visceral metastasis, and poor performance status. Also, they noted, 61% of the screened patients received cisplatin chemotherapy, and 48% had visceral metastasis, “which gives some insight into the current population of patients who receive chemotherapy.”

GlaxoSmithKline and Cancer Research U.K. sponsored the study. Dr. Powles and several coauthors disclosed financial support from GlaxoSmithKline and other pharmaceutical firms.

Patients with metastatic urothelial bladder cancer (UBC) overexpressing HER1 or HER2 did not benefit from a course of lapatinib maintenance therapy following chemotherapy, a U.K.-based research group reported.

The phase III study, led by Thomas Powles, MD, of Queen Mary University of London, randomized 232 patients (mean age 71, about 75% male) with HER1- or HER2-positive metastatic UBC who had not progressed during platinum-based chemotherapy to placebo or lapatinib (Tykerb), an oral medication that targets HER1 and HER2 and is marketed for use in some breast cancers. The lapatinib-treated group saw no significant gains in either progression-free (PFS) or overall survival (OS), Dr. Powles and associates reported (J Clin Oncol. 2016 Oct 31. doi: 10.1200/JCO.2015.66.3468).

The median PFS for patients receiving lapatinib 1,500 mg daily was 4.5 months, compared with 5.1 months for the placebo group (hazard ratio, 1.07; 95% CI, 0.81-1.43; P = .63), while OS after chemotherapy was 12.6 and 12 months, respectively (HR 0.96; 95% CI, 0.70-1.31; P = .80). A subgroup of patients strongly positive for either or both receptors did not see significant OS or PFS benefit associated with lapatinib, a finding that the investigators said reinforced a lack of benefit.

While previous studies have indicated roles for both HER1 and HER2 in bladder cancer progression, targeting them “may not be of clinical benefit in UBC,” Dr. Powles and his colleagues wrote.

Patients with metastatic UBC have short overall survival following first-line chemotherapy, and few proven second-line treatment options exist besides additional chemotherapy, whose benefit is controversial, the researchers noted.

Despite this trial’s negative result for postchemotherapy maintenance treatment with lapatinib, Dr. Powles and his colleagues said their study, which screened 446 patients with metastatic UBC before randomizing slightly more than half, nonetheless shed some light on this difficult-to-treat patient group, including identifying three prognostic factors associated with poor outcome: radiologic progression during chemotherapy, visceral metastasis, and poor performance status. Also, they noted, 61% of the screened patients received cisplatin chemotherapy, and 48% had visceral metastasis, “which gives some insight into the current population of patients who receive chemotherapy.”

GlaxoSmithKline and Cancer Research U.K. sponsored the study. Dr. Powles and several coauthors disclosed financial support from GlaxoSmithKline and other pharmaceutical firms.

Patients with metastatic urothelial bladder cancer (UBC) overexpressing HER1 or HER2 did not benefit from a course of lapatinib maintenance therapy following chemotherapy, a U.K.-based research group reported.

The phase III study, led by Thomas Powles, MD, of Queen Mary University of London, randomized 232 patients (mean age 71, about 75% male) with HER1- or HER2-positive metastatic UBC who had not progressed during platinum-based chemotherapy to placebo or lapatinib (Tykerb), an oral medication that targets HER1 and HER2 and is marketed for use in some breast cancers. The lapatinib-treated group saw no significant gains in either progression-free (PFS) or overall survival (OS), Dr. Powles and associates reported (J Clin Oncol. 2016 Oct 31. doi: 10.1200/JCO.2015.66.3468).

The median PFS for patients receiving lapatinib 1,500 mg daily was 4.5 months, compared with 5.1 months for the placebo group (hazard ratio, 1.07; 95% CI, 0.81-1.43; P = .63), while OS after chemotherapy was 12.6 and 12 months, respectively (HR 0.96; 95% CI, 0.70-1.31; P = .80). A subgroup of patients strongly positive for either or both receptors did not see significant OS or PFS benefit associated with lapatinib, a finding that the investigators said reinforced a lack of benefit.

While previous studies have indicated roles for both HER1 and HER2 in bladder cancer progression, targeting them “may not be of clinical benefit in UBC,” Dr. Powles and his colleagues wrote.

Patients with metastatic UBC have short overall survival following first-line chemotherapy, and few proven second-line treatment options exist besides additional chemotherapy, whose benefit is controversial, the researchers noted.

Despite this trial’s negative result for postchemotherapy maintenance treatment with lapatinib, Dr. Powles and his colleagues said their study, which screened 446 patients with metastatic UBC before randomizing slightly more than half, nonetheless shed some light on this difficult-to-treat patient group, including identifying three prognostic factors associated with poor outcome: radiologic progression during chemotherapy, visceral metastasis, and poor performance status. Also, they noted, 61% of the screened patients received cisplatin chemotherapy, and 48% had visceral metastasis, “which gives some insight into the current population of patients who receive chemotherapy.”

GlaxoSmithKline and Cancer Research U.K. sponsored the study. Dr. Powles and several coauthors disclosed financial support from GlaxoSmithKline and other pharmaceutical firms.