Early Results Favor Trastuzumab-DM1 in Randomized Breast Cancer Trial

Trastuzumab-DM1 produced higher response rates with less toxicity than did a combination of trastuzumab and docetaxel in the first randomized trial of the novel agent as first-line therapy for metastatic HER2-positive breast cancer.

At a median six months’ follow-up, overall response rates were 48% in the trastuzumab-DM1 (T-DM1) arm and 41% in the trastuzumab (Herceptin) – docetaxel (Taxotere) arm of the open-label phase II trial. Three of 67 women treated with the novel drug had complete responses, compared with 1 of 70 women given trastuzumab and docetaxel.

Serious adverse events of grade 3 or higher in the T-DM1 arm were about half as frequent with T-DM1 as in the control arm (37% vs. 75%), but 1 treatment-related death was reported in the experimental arm. The most common adverse events were nausea, fatigue, and pyrexia in women treated with T-DM1.

Dr. Edith Perez of the Mayo Clinic in Jacksonville, Fla. will report the preliminary data Oct. 11 in Milan at the annual meeting of the European Society for Clinical Oncology. A professor of medicine at the Mayo Medical School, she is principal investigator of the ongoing study. A larger three-armed phase III trial called MARIANNE is comparing T-DM1 monotherapy to trastuzumab plus a taxane and to T-DM1 plus pertuzumab, which also targets HER2.

The Food and Drug Administration recently refused a request from Roche to fast-track T-DM1 based on positive single-arm studies. Although the women in those studies had been heavily pretreated, the agency said they had not exhausted all options.

T-DM1 combines two lines of attack in one agent: the anti-HER2 activity of trastuzumab, a monoclonal antibody, with the targeted intracellular delivery of DM1, a potent antimicrotubule agent. The DM1 component is licensed by ImmunoGen, Inc.

In a press statement, Dr. Fabrice Andr? from Institut Gustave Roussy in Villejuif, France, described the results to be reported by Dr. Perez as important for two reasons.

“Firstly, they confirm that in coming years chemotherapy could be replaced by a less toxic compound .... These results suggest that, with the same efficacy, T-DM1 could dramatically reduce the toxicities related to chemotherapy."”

Secondly, Dr. Andr? observed that the study offers proof of concept for the linking of a monoclonal antibody to a cytotoxic drug in an anti-cancer therapy. “This could have several implications beyond drugs that target HER2,” Dr Andr? said.

Dr. Perez declared no conflicts of interest. Several of her coauthors disclosed receiving research support from Roche/Genentech and three identified themselves as employees and stockholders of Roche.☐

Trastuzumab-DM1 produced higher response rates with less toxicity than did a combination of trastuzumab and docetaxel in the first randomized trial of the novel agent as first-line therapy for metastatic HER2-positive breast cancer.

At a median six months’ follow-up, overall response rates were 48% in the trastuzumab-DM1 (T-DM1) arm and 41% in the trastuzumab (Herceptin) – docetaxel (Taxotere) arm of the open-label phase II trial. Three of 67 women treated with the novel drug had complete responses, compared with 1 of 70 women given trastuzumab and docetaxel.

Serious adverse events of grade 3 or higher in the T-DM1 arm were about half as frequent with T-DM1 as in the control arm (37% vs. 75%), but 1 treatment-related death was reported in the experimental arm. The most common adverse events were nausea, fatigue, and pyrexia in women treated with T-DM1.

Dr. Edith Perez of the Mayo Clinic in Jacksonville, Fla. will report the preliminary data Oct. 11 in Milan at the annual meeting of the European Society for Clinical Oncology. A professor of medicine at the Mayo Medical School, she is principal investigator of the ongoing study. A larger three-armed phase III trial called MARIANNE is comparing T-DM1 monotherapy to trastuzumab plus a taxane and to T-DM1 plus pertuzumab, which also targets HER2.

The Food and Drug Administration recently refused a request from Roche to fast-track T-DM1 based on positive single-arm studies. Although the women in those studies had been heavily pretreated, the agency said they had not exhausted all options.

T-DM1 combines two lines of attack in one agent: the anti-HER2 activity of trastuzumab, a monoclonal antibody, with the targeted intracellular delivery of DM1, a potent antimicrotubule agent. The DM1 component is licensed by ImmunoGen, Inc.

In a press statement, Dr. Fabrice Andr? from Institut Gustave Roussy in Villejuif, France, described the results to be reported by Dr. Perez as important for two reasons.

“Firstly, they confirm that in coming years chemotherapy could be replaced by a less toxic compound .... These results suggest that, with the same efficacy, T-DM1 could dramatically reduce the toxicities related to chemotherapy."”

Secondly, Dr. Andr? observed that the study offers proof of concept for the linking of a monoclonal antibody to a cytotoxic drug in an anti-cancer therapy. “This could have several implications beyond drugs that target HER2,” Dr Andr? said.

Dr. Perez declared no conflicts of interest. Several of her coauthors disclosed receiving research support from Roche/Genentech and three identified themselves as employees and stockholders of Roche.☐

Trastuzumab-DM1 produced higher response rates with less toxicity than did a combination of trastuzumab and docetaxel in the first randomized trial of the novel agent as first-line therapy for metastatic HER2-positive breast cancer.

At a median six months’ follow-up, overall response rates were 48% in the trastuzumab-DM1 (T-DM1) arm and 41% in the trastuzumab (Herceptin) – docetaxel (Taxotere) arm of the open-label phase II trial. Three of 67 women treated with the novel drug had complete responses, compared with 1 of 70 women given trastuzumab and docetaxel.

Serious adverse events of grade 3 or higher in the T-DM1 arm were about half as frequent with T-DM1 as in the control arm (37% vs. 75%), but 1 treatment-related death was reported in the experimental arm. The most common adverse events were nausea, fatigue, and pyrexia in women treated with T-DM1.

Dr. Edith Perez of the Mayo Clinic in Jacksonville, Fla. will report the preliminary data Oct. 11 in Milan at the annual meeting of the European Society for Clinical Oncology. A professor of medicine at the Mayo Medical School, she is principal investigator of the ongoing study. A larger three-armed phase III trial called MARIANNE is comparing T-DM1 monotherapy to trastuzumab plus a taxane and to T-DM1 plus pertuzumab, which also targets HER2.

The Food and Drug Administration recently refused a request from Roche to fast-track T-DM1 based on positive single-arm studies. Although the women in those studies had been heavily pretreated, the agency said they had not exhausted all options.

T-DM1 combines two lines of attack in one agent: the anti-HER2 activity of trastuzumab, a monoclonal antibody, with the targeted intracellular delivery of DM1, a potent antimicrotubule agent. The DM1 component is licensed by ImmunoGen, Inc.

In a press statement, Dr. Fabrice Andr? from Institut Gustave Roussy in Villejuif, France, described the results to be reported by Dr. Perez as important for two reasons.

“Firstly, they confirm that in coming years chemotherapy could be replaced by a less toxic compound .... These results suggest that, with the same efficacy, T-DM1 could dramatically reduce the toxicities related to chemotherapy."”

Secondly, Dr. Andr? observed that the study offers proof of concept for the linking of a monoclonal antibody to a cytotoxic drug in an anti-cancer therapy. “This could have several implications beyond drugs that target HER2,” Dr Andr? said.

Dr. Perez declared no conflicts of interest. Several of her coauthors disclosed receiving research support from Roche/Genentech and three identified themselves as employees and stockholders of Roche.☐