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Adding trastuzumab to carboplatin/paclitaxel improved survival in patients with advanced or recurrent HER2/Neu-positive uterine serous carcinoma (USC), according to an updated analysis from a phase 2 trial.
At a median follow-up of 25.9 months, the median progression-free survival (PFS) was 12.9 months in patients who received trastuzumab plus carboplatin/paclitaxel and 8.0 months in patients who received only carboplatin/paclitaxel. The median overall survival (OS) was 29.6 months and 24.4 months, respectively.
Amanda Nickles Fader, MD, of Johns Hopkins Medicine, Baltimore, and colleagues reported these findings in an abstract that was slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic.
Confirmed benefit
The phase 2 trial was designed to assess whether trastuzumab, a humanized monoclonal antibody that targets HER2/neu – a growth factor receptor found in almost all USC cases and overexpressed in 30% of cases – would improve survival in patients with USC, Dr. Nickles Fader explained in an interview. She noted that trastuzumab has been shown to provide benefit in breast cancer patients with HER2/neu overexpression.
“[U]terine serous carcinoma ... is a very aggressive high-grade endometrial cancer subtype that is associated with really poor clinical outcomes and significant mortality,” Dr. Nickles Fader said. “It represents fewer than 10% of all uterine cancer cases, but it actually accounts for a disproportionate 40% of all deaths from uterine cancer.”
The overall survival among USC patients is about 45%, compared with 91% for more common lower-grade types of uterine cancers, she added.
“The conventional treatments for uterine serous carcinoma include surgery and then chemotherapy, but we’ve only really gotten so far by using a sort of one-size-fits-all treatment philosophy,” Dr. Nickles Fader said.
Based on preliminary findings from the current trial (J Clin Oncol. 2018 Jul 10;36[20]:2044-51), trastuzumab plus carboplatin/paclitaxel is now recognized as an alternative standard in treating advanced or recurrent HER2/Neu-positive USC, and this updated analysis confirms the benefits of adding trastuzumab, she said.
PFS, OS, and toxicity
There were 58 evaluable patients with primary stage III-IV or recurrent USC who were randomized to receive six cycles of carboplatin/paclitaxel alone or in combination with intravenous trastuzumab given until toxicity or progression.
The median PFS at a median follow-up of 25.9 months “very significantly favored” the trastuzumab arm, Dr. Nickles Fader said. The median PFS was 12.9 months in the trastuzumab arm and 8.0 months in the carboplatin/paclitaxel arm (hazard ratio, 0.46; P = .005).
In the 41 patients undergoing primary treatment, the median PFS was 17.7 months in the trastuzumab arm and 9.3 months in the control arm (HR, 0.44; P = .015). In the 17 patients with recurrent disease, the median PFS was 9.2 months and 7.0 months, respectively (HR, 0.12; P = .004).
“We were very pleased to see that there was also an overall survival benefit of about 5 months in the trastuzumab arm, compared to the control arm,” Dr. Nickles Fader said. The median OS was 29.6 months and 24.4 months, respectively (HR, 0.58; P = .046).
The PFS and OS benefit was “particularly striking” in the stage III-IV patients, according to Dr. Nickles Fader and colleagues. In this subgroup, the median OS was not reached in the trastuzumab arm, and it was 25.4 months in the control arm (HR, 0.49; P = .041).
Long-term toxicity did not differ between the treatment arms.
Applications and next steps
“The take-home message here is women should be tested if they have this subtype,” Dr. Nickles Fader said. “If they’re newly diagnosed, they should be tested for the HER2/neu receptor, and if [it is overexpressed] and they have advanced disease, we do recommend treatment with not only the conventional treatment, but with trastuzumab added to that, because that’s where we saw the most benefit.”
This is the only trial that has ever shown a major PFS and OS difference with combination targeted therapy and conventional chemotherapy in USC, Dr. Nickles Fader noted.
“So it was really exciting to see that,” she said, adding that a “much larger cooperative group trial” is being designed by the National Cancer Institute and NRG Oncology Group to look at this approach in HER2-positive, advanced-stage uterine cancers. The trial will include patients with USC, but it will extend to other uterine cancer types as well.
“We’re looking at different combinations of anti-HER2 therapies to sort of validate the results of this trial, but also to study this in other tumors that are HER2 positive,” Dr. Nickles Fader explained.
She also stressed the importance of addressing racial disparities in survival among women with USC, as African American women have higher rates of USC and related mortality than do other groups.
“It’s going to be important to look at not only molecular targets and improving survival but also racial inequalities and potentially epigenetics to really improve survival across the board,” Dr. Nickles Fader said.
She reported having no disclosures. The trial was sponsored by Yale University in collaboration with Genentech.
SOURCE: Nickles Fader A et al. SGO 2020, Abstract 12.
Adding trastuzumab to carboplatin/paclitaxel improved survival in patients with advanced or recurrent HER2/Neu-positive uterine serous carcinoma (USC), according to an updated analysis from a phase 2 trial.
At a median follow-up of 25.9 months, the median progression-free survival (PFS) was 12.9 months in patients who received trastuzumab plus carboplatin/paclitaxel and 8.0 months in patients who received only carboplatin/paclitaxel. The median overall survival (OS) was 29.6 months and 24.4 months, respectively.
Amanda Nickles Fader, MD, of Johns Hopkins Medicine, Baltimore, and colleagues reported these findings in an abstract that was slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic.
Confirmed benefit
The phase 2 trial was designed to assess whether trastuzumab, a humanized monoclonal antibody that targets HER2/neu – a growth factor receptor found in almost all USC cases and overexpressed in 30% of cases – would improve survival in patients with USC, Dr. Nickles Fader explained in an interview. She noted that trastuzumab has been shown to provide benefit in breast cancer patients with HER2/neu overexpression.
“[U]terine serous carcinoma ... is a very aggressive high-grade endometrial cancer subtype that is associated with really poor clinical outcomes and significant mortality,” Dr. Nickles Fader said. “It represents fewer than 10% of all uterine cancer cases, but it actually accounts for a disproportionate 40% of all deaths from uterine cancer.”
The overall survival among USC patients is about 45%, compared with 91% for more common lower-grade types of uterine cancers, she added.
“The conventional treatments for uterine serous carcinoma include surgery and then chemotherapy, but we’ve only really gotten so far by using a sort of one-size-fits-all treatment philosophy,” Dr. Nickles Fader said.
Based on preliminary findings from the current trial (J Clin Oncol. 2018 Jul 10;36[20]:2044-51), trastuzumab plus carboplatin/paclitaxel is now recognized as an alternative standard in treating advanced or recurrent HER2/Neu-positive USC, and this updated analysis confirms the benefits of adding trastuzumab, she said.
PFS, OS, and toxicity
There were 58 evaluable patients with primary stage III-IV or recurrent USC who were randomized to receive six cycles of carboplatin/paclitaxel alone or in combination with intravenous trastuzumab given until toxicity or progression.
The median PFS at a median follow-up of 25.9 months “very significantly favored” the trastuzumab arm, Dr. Nickles Fader said. The median PFS was 12.9 months in the trastuzumab arm and 8.0 months in the carboplatin/paclitaxel arm (hazard ratio, 0.46; P = .005).
In the 41 patients undergoing primary treatment, the median PFS was 17.7 months in the trastuzumab arm and 9.3 months in the control arm (HR, 0.44; P = .015). In the 17 patients with recurrent disease, the median PFS was 9.2 months and 7.0 months, respectively (HR, 0.12; P = .004).
“We were very pleased to see that there was also an overall survival benefit of about 5 months in the trastuzumab arm, compared to the control arm,” Dr. Nickles Fader said. The median OS was 29.6 months and 24.4 months, respectively (HR, 0.58; P = .046).
The PFS and OS benefit was “particularly striking” in the stage III-IV patients, according to Dr. Nickles Fader and colleagues. In this subgroup, the median OS was not reached in the trastuzumab arm, and it was 25.4 months in the control arm (HR, 0.49; P = .041).
Long-term toxicity did not differ between the treatment arms.
Applications and next steps
“The take-home message here is women should be tested if they have this subtype,” Dr. Nickles Fader said. “If they’re newly diagnosed, they should be tested for the HER2/neu receptor, and if [it is overexpressed] and they have advanced disease, we do recommend treatment with not only the conventional treatment, but with trastuzumab added to that, because that’s where we saw the most benefit.”
This is the only trial that has ever shown a major PFS and OS difference with combination targeted therapy and conventional chemotherapy in USC, Dr. Nickles Fader noted.
“So it was really exciting to see that,” she said, adding that a “much larger cooperative group trial” is being designed by the National Cancer Institute and NRG Oncology Group to look at this approach in HER2-positive, advanced-stage uterine cancers. The trial will include patients with USC, but it will extend to other uterine cancer types as well.
“We’re looking at different combinations of anti-HER2 therapies to sort of validate the results of this trial, but also to study this in other tumors that are HER2 positive,” Dr. Nickles Fader explained.
She also stressed the importance of addressing racial disparities in survival among women with USC, as African American women have higher rates of USC and related mortality than do other groups.
“It’s going to be important to look at not only molecular targets and improving survival but also racial inequalities and potentially epigenetics to really improve survival across the board,” Dr. Nickles Fader said.
She reported having no disclosures. The trial was sponsored by Yale University in collaboration with Genentech.
SOURCE: Nickles Fader A et al. SGO 2020, Abstract 12.
Adding trastuzumab to carboplatin/paclitaxel improved survival in patients with advanced or recurrent HER2/Neu-positive uterine serous carcinoma (USC), according to an updated analysis from a phase 2 trial.
At a median follow-up of 25.9 months, the median progression-free survival (PFS) was 12.9 months in patients who received trastuzumab plus carboplatin/paclitaxel and 8.0 months in patients who received only carboplatin/paclitaxel. The median overall survival (OS) was 29.6 months and 24.4 months, respectively.
Amanda Nickles Fader, MD, of Johns Hopkins Medicine, Baltimore, and colleagues reported these findings in an abstract that was slated for presentation at the Society of Gynecologic Oncology’s Annual Meeting on Women’s Cancer. The meeting was canceled because of the COVID-19 pandemic.
Confirmed benefit
The phase 2 trial was designed to assess whether trastuzumab, a humanized monoclonal antibody that targets HER2/neu – a growth factor receptor found in almost all USC cases and overexpressed in 30% of cases – would improve survival in patients with USC, Dr. Nickles Fader explained in an interview. She noted that trastuzumab has been shown to provide benefit in breast cancer patients with HER2/neu overexpression.
“[U]terine serous carcinoma ... is a very aggressive high-grade endometrial cancer subtype that is associated with really poor clinical outcomes and significant mortality,” Dr. Nickles Fader said. “It represents fewer than 10% of all uterine cancer cases, but it actually accounts for a disproportionate 40% of all deaths from uterine cancer.”
The overall survival among USC patients is about 45%, compared with 91% for more common lower-grade types of uterine cancers, she added.
“The conventional treatments for uterine serous carcinoma include surgery and then chemotherapy, but we’ve only really gotten so far by using a sort of one-size-fits-all treatment philosophy,” Dr. Nickles Fader said.
Based on preliminary findings from the current trial (J Clin Oncol. 2018 Jul 10;36[20]:2044-51), trastuzumab plus carboplatin/paclitaxel is now recognized as an alternative standard in treating advanced or recurrent HER2/Neu-positive USC, and this updated analysis confirms the benefits of adding trastuzumab, she said.
PFS, OS, and toxicity
There were 58 evaluable patients with primary stage III-IV or recurrent USC who were randomized to receive six cycles of carboplatin/paclitaxel alone or in combination with intravenous trastuzumab given until toxicity or progression.
The median PFS at a median follow-up of 25.9 months “very significantly favored” the trastuzumab arm, Dr. Nickles Fader said. The median PFS was 12.9 months in the trastuzumab arm and 8.0 months in the carboplatin/paclitaxel arm (hazard ratio, 0.46; P = .005).
In the 41 patients undergoing primary treatment, the median PFS was 17.7 months in the trastuzumab arm and 9.3 months in the control arm (HR, 0.44; P = .015). In the 17 patients with recurrent disease, the median PFS was 9.2 months and 7.0 months, respectively (HR, 0.12; P = .004).
“We were very pleased to see that there was also an overall survival benefit of about 5 months in the trastuzumab arm, compared to the control arm,” Dr. Nickles Fader said. The median OS was 29.6 months and 24.4 months, respectively (HR, 0.58; P = .046).
The PFS and OS benefit was “particularly striking” in the stage III-IV patients, according to Dr. Nickles Fader and colleagues. In this subgroup, the median OS was not reached in the trastuzumab arm, and it was 25.4 months in the control arm (HR, 0.49; P = .041).
Long-term toxicity did not differ between the treatment arms.
Applications and next steps
“The take-home message here is women should be tested if they have this subtype,” Dr. Nickles Fader said. “If they’re newly diagnosed, they should be tested for the HER2/neu receptor, and if [it is overexpressed] and they have advanced disease, we do recommend treatment with not only the conventional treatment, but with trastuzumab added to that, because that’s where we saw the most benefit.”
This is the only trial that has ever shown a major PFS and OS difference with combination targeted therapy and conventional chemotherapy in USC, Dr. Nickles Fader noted.
“So it was really exciting to see that,” she said, adding that a “much larger cooperative group trial” is being designed by the National Cancer Institute and NRG Oncology Group to look at this approach in HER2-positive, advanced-stage uterine cancers. The trial will include patients with USC, but it will extend to other uterine cancer types as well.
“We’re looking at different combinations of anti-HER2 therapies to sort of validate the results of this trial, but also to study this in other tumors that are HER2 positive,” Dr. Nickles Fader explained.
She also stressed the importance of addressing racial disparities in survival among women with USC, as African American women have higher rates of USC and related mortality than do other groups.
“It’s going to be important to look at not only molecular targets and improving survival but also racial inequalities and potentially epigenetics to really improve survival across the board,” Dr. Nickles Fader said.
She reported having no disclosures. The trial was sponsored by Yale University in collaboration with Genentech.
SOURCE: Nickles Fader A et al. SGO 2020, Abstract 12.
FROM SGO 2020