Ado-trastuzumab for the treatment of metastatic HER2-positive breast cancer in patients previously treated with Pertuzumab

Abstract Background Docetaxel in combination with two HER2-directed therapies, trastuzumab and pertuzumab, is the current standard frontline therapy for patients with metastatic HER2-positive breast cancer. Ado-trastuzumab (T-DM1), an antibody-drug conjugate of trastuzumab and a cytotoxic microtubule-inhibitory agent, emtansine, is approved in patients that have progressed with prior trastuzumab-based therapy. However, the benefit of T-DM1 in patients previously treated with pertuzumab therapy for metastatic breast cancer remains unclear. Methods We identified thirty-three adults with metastatic HER2-positive breast cancer treated between March 2013 and July 2018 with T-DM1 either as subsequent therapy after progression on a pertuzumab-based regimen (i.e., “pertuzumab-pretreated”) or without prior exposure to pertuzumab (i.e., “pertuzumab-naïve”). Collected data included patient demographics, treatment history, adverse events, and clinical outcomes. For both cohorts receiving T-DM1, the primary endpoint was PFS and secondary endpoints were overall survival (OS), overall response rate (ORR), clinical benefit rate (CBR), and T-DM1-related toxicity rate. Results Pertuzumab-pretreated patients (n = 23, with 21 evaluable for T-DM1 efficacy) had a median PFS of 9.5 months (95% CI: 2.9–NA), 1-year OS rate of 67.4% (95% CI: 50.0–90.9%) with an unreached median, ORR of 14.3% (95% CI: 3.0–36.3%), and CBR of 52.4% (95% CI: 29.8–74.3%), with none of these measures being statistically different than those estimated for the pertuzumab-naïve group (n = 10). Treatment with T-DM1 after prior pertuzumab exposure (median T-DM1 duration 2.9 months) resulted in no grade ≥ 3 adverse events. Conclusions In our cohort, prior exposure to pertuzumab did not significantly impact T-DM1’s clinical efficacy or safety profile as second- or later-line therapy in patients with metastatic HER2-positive breast cancer.

Download Full-text

Ado-trastuzumab for the Treatment of Metastatic HER2-Positive Breast Cancer in Patients Previously Treated with Pertuzumab

10.21203/rs.3.rs-353585/v1 ◽

2021 ◽

Author(s):

Luai Al Rabadi ◽

Madeline Cook ◽

Andy Kaempf ◽

Megan Saraceni ◽

Michael Savin ◽

...

Keyword(s):

Breast Cancer ◽

Adverse Events ◽

Metastatic Breast ◽

Prior Exposure ◽

Current Standard ◽

Antibody Drug Conjugate ◽

Her2 Positive ◽

Her2 Positive Breast Cancer ◽

Previously Treated ◽

Positive Breast Cancer

Abstract Background: Docetaxel in combination with two HER2-directed therapies, trastuzumab and pertuzumab, is the current standard frontline therapy for patients with metastatic HER2-positive breast cancer. Ado-trastuzumab (T-DM1), an antibody-drug conjugate of trastuzumab and a cytotoxic microtubule-inhibitory agent, emtansine, is approved in patients that have progressed with prior trastuzumab-based therapy. However, the benefit of T-DM1 in patients previously treated with pertuzumab therapy for metastatic breast cancer remains unclear.Methods: We identified thirty-three adults with metastatic HER2-positive breast cancer treated between March 2013 and July 2018 with T-DM1 either as subsequent therapy after progression on a pertuzumab-based regimen (i.e., “pertuzumab-pretreated”) or without prior exposure to pertuzumab (i.e., “pertuzumab-naïve”). Collected data included patient demographics, treatment history, adverse events, and clinical outcomes. For both cohorts receiving T-DM1, the primary endpoint was PFS and secondary endpoints were overall survival (OS), overall response rate (ORR), clinical benefit rate (CBR), and T-DM1-related toxicity rate.Results: Pertuzumab-pretreated patients (n=23, with 21 evaluable for T-DM1 efficacy) had a median PFS of 9.5 months (95% CI: 2.9–NA), 1-year OS rate of 67.4% (95% CI: 50.0%–90.9%) with an unreached median, ORR of 14.3% (95% CI: 3.0%–36.3%), and CBR of 52.4% (95% CI: 29.8%–74.3%), with none of these measures being statistically different than those estimated for the pertuzumab-naïve group (n=10). Treatment with T-DM1 after prior pertuzumab exposure (median T-DM1 duration 2.9 months) resulted in no grade ≥ 3 adverse events.Conclusions: Prior exposure to pertuzumab did not impact survival outcomes in patients receiving T-DM1 for metastatic HER2-positive breast cancer.

Download Full-text

Trastuzumab deruxtecan in previously treated HER2-positive metastatic breast cancer: Plain language summary of the DESTINY-Breast01 study

Future Oncology ◽

10.2217/fon-2021-0427 ◽

2021 ◽

Author(s):

Shanu Modi

Keyword(s):

Breast Cancer ◽

Adverse Events ◽

Metastatic Breast ◽

Common Adverse Event ◽

The Body ◽

Plain Language ◽

Her2 Positive ◽

Serious Adverse Events ◽

Her2 Positive Breast Cancer ◽

Positive Breast Cancer

This is a summary of the article discussing the results of the DESTINY-Breast01 study originally published in the New England Journal of Medicine. The DESTINY-Breast01 study is a clinical study in participants with a type of breast cancer called HER2-positive breast cancer. The participants in the study received a treatment called trastuzumab deruxtecan, also known as T-DXd. The purpose of this summary is to help you understand the results of the DESTINY-Breast01 study. T-DXd is currently available as a treatment for adults with HER2-positive breast cancer that cannot be removed by surgery, also called unresectable, or that has spread, also called metastatic. In the DESTINY-Breast01 study, all the participants had HER2-positive breast cancer that was metastatic or unresectable. All participants were required to have had previous treatment for their HER2-positive breast cancer with another treatment, called trastuzumab emtansine or T-DM1. All the participants received T-DXd every 3 weeks. Part 1 was done to learn how T-DXd acted in the body, and to choose a dose to give to all the participants in Part 2. In Part 2, 184 participants received T-DXd at 5.4 mg/kg and the results showed that T-DXd reduced tumor growth. Up to 60.9% of the participants had their tumors shrink or disappear, with a treatment response that lasted for nearly 15 months on average. The participants lived with their cancer for around 16 months before it got worse. During the study, 183 out of 184 participants had side effects, known as adverse events. The most common adverse event was nausea. There were 42 participants (22.8%) who had serious adverse events, including lung toxicity. These results suggest that T-DXd could be a treatment option for people with metastatic HER2-positive breast cancer who have already been treated with T-DM1. Additional studies will provide more information and results about T-DXd. ClinicalTrials.gov NCT number: NCT03248492 To read the full Plain Language Summary of this article, click on the View Article button above and download the PDF. Link to original article here .

Download Full-text

New Therapeutic Strategies in Advanced Nonoperable or Metastatic HER2-positive Breast Cancer

Geburtshilfe und Frauenheilkunde ◽

10.1055/a-1471-4063 ◽

2021 ◽

Vol 81 (06) ◽

pp. 666-678

Author(s):

Diana Lüftner ◽

Matthias Peipp

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Treatment Options ◽

Metastatic Breast ◽

Antibody Engineering ◽

Antibody Drug Conjugate ◽

Her2 Positive ◽

Her2 Positive Breast Cancer ◽

The Us ◽

Positive Breast Cancer

AbstractDespite therapeutic gains in the treatment of HER2-positive (HER2: human epidermal growth factor receptor 2) advanced/metastatic breast cancer, there remains an urgent need for more effective treatment options. At present, there is no definitive approved standard therapy beyond second-line treatment. One of the major challenges is overcoming treatment resistance. Depending on the underlying resistance mechanism, different strategies are being pursued for new innovative treatment concepts in HER2-positive breast cancer. Specifically designed antibodies for targeted therapy are one important focus to successfully meet these challenges. Trastuzumab deruxtecan (T-DXd, DS-8201a), an optimised antibody drug conjugate (ADC) is in clinical trials, showing promising outcomes in patients with advanced, nonoperable or metastatic HER2-positive breast cancer who had already undergone intensive prior treatment. Based on this data, T-DXd has already been approved in the US and Japan for HER2-positive advanced nonoperable and metastatic breast cancer – in the US after at least two prior anti-HER2 targeted treatment lines and in Japan after prior chemotherapy. T-DXd represents successful “antibody engineering”. Since the beginning of the year, T-DXd has also been approved in Europe as monotherapy for inoperable or metastatic HER2-positive breast cancer in patients who are pretreated with at least two anti-HER2 directed therapies. This paper presents strategies for improving treatment options in advanced nonoperable and metastatic HER2-positive breast cancer, with the development of T-DXd as an example.

Download Full-text

Faculty Opinions recommendation of Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.737064269.793568624 ◽

2019 ◽

Author(s):

Giuseppe Curigliano

Keyword(s):

Breast Cancer ◽

Her2 Positive ◽

Her2 Positive Breast Cancer ◽

Previously Treated ◽

Positive Breast Cancer

Download Full-text

Real-world effectiveness of post-trastuzumab emtansine treatment in patients with HER2-positive, unresectable and/or metastatic breast cancer: a retrospective observational study (KBCSG-TR 1917)

BMC Cancer ◽

10.1186/s12885-021-08504-1 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Takahiro Nakayama ◽

Tetsuhiro Yoshinami ◽

Hiroyuki Yasojima ◽

Nobuyoshi Kittaka ◽

Masato Takahashi ◽

...

Keyword(s):

Breast Cancer ◽

Metastatic Breast Cancer ◽

Observational Study ◽

Real World ◽

Metastatic Breast ◽

Trastuzumab Emtansine ◽

Her2 Positive ◽

The Real ◽

Her2 Positive Breast Cancer ◽

Positive Breast Cancer

Abstract Background Trastuzumab emtansine (T-DM1) is a second-line standard therapy for patients with human epidermal growth factor receptor 2 (HER2)-positive metastatic breast cancer. Evidence regarding post–T-DM1 treatments is currently lacking. We evaluated the effectiveness of post–T-DM1 drug therapy in patients with HER2-positive, unresectable and/or metastatic breast cancer. Methods In this multicenter, retrospective, observational study, real-world clinical data of female patients with HER2-positive breast cancer who had a history of T-DM1 treatment were consecutively collected from five sites in Japan. We investigated the effectiveness of post–T-DM1 therapy by evaluating the real-world progression-free survival (rwPFS), time to treatment failure (TTF), overall survival (OS), objective response rate (ORR), and clinical benefit rate (CBR). Tumor response was assessed by investigators according to Response Evaluation Criteria in Solid Tumors (RECIST version 1.1) guidelines. Subgroup and exploratory analyses according to background factors were also undertaken. Results Of the 205 patients who received T-DM1 treatment between 1 January 2014 and 31 December 2018, 128 were included in this study. Among the 128 patients analyzed, 105 (82%) patients received anti-HER2 therapy and 23 (18%) patients received regimens without anti-HER2 therapy. Median (95% confidence interval [CI]) rwPFS, TTF, and OS were 5.7 (4.8–6.9) months, 5.6 (4.6–6.4) months, and 22.8 (18.2–32.4) months, respectively. CBR and ORR (95% CI) were 48% (38.8–56.7) and 23% (15.1–31.4), respectively. Cox-regression analysis showed that an ECOG PS score of 0, a HER2 immunohistochemistry score of 3+, recurrent type, ≥12 month duration of T-DM1 therapy, and anti-HER2 therapy were independent variables for rwPFS. An exploratory subgroup analysis of regimens after T-DM1 showed that those with anti-HER2 therapy had a median rwPFS of 6.3 and those without anti-HER2 therapy had a median rwPFS of 4.8 months. Conclusions In the real-world setting in Japan, several post–T-DM1 regimens for patients with unresectable and/or metastatic HER2-positive breast cancer, including continuation of anti-HER2 therapy, showed some effectiveness; however, this effectiveness was insufficient. Novel therapeutic options are still needed for further improvement of PFS and OS in later treatment settings. Trial registration UMIN000038296; registered on 15 October 2019.

Download Full-text