• Published in parallel in The New England Journal of Medicine*, data from two phase II studies presented yesterday at the San Antonio Breast Cancer Symposium – SABCS (10 – 14 December, San Antonio, Texas, USA), driven in collaboration with VHIO, promise new hope for the treatment of metastatic HER2-postive breast cancer.

 

  • Breaking new ground, half of the patients included in this multinational phase II study had brain metastases, a patient population typically under-represented in clinical trials.The investigators assessed the efficacy of the triplet combination of tucatinib, trastuzumab and capecitabine,  based on increased progression-free survival or increased overall survival.

 

  • The DESTINY-Breast01 pivotal phase II trial sought to assess the efficacy of second generation  trastuzumab  deruxtecan in heavily pre-treated patients with HER2+ metastatic breast cancer

 

Despite the indisputable progress made over recent years in improving outcomes for breast cancer patients, this tumor type remains the most common cancer and one of the principal causes of cancer mortality in women. Of the 2 million new cases diagnosed worldwide in 2018, an estimated 15-20% of these will have been classified as HER2-positive.

Up until relatively recently, this subtype had one of the most dismal prognoses of all cancers. Fortunately, the subsequent development and approval of more potent and effective therapies has completely revolutionized the treatment landscape for this population of patients. Despite such progress, however, two main challenges remain. They are, acquired resistance to anti-cancer medicines and metastatic cell spread.

Covering important ground in tackling these obstacles and potentially marking progress in the ‘chronification’ of advanced, HER2+ refractory breast cancer, results from two studies, HER2CLIMB and DESTINY-Breast01, were reported at the same General Session** yesterday at SABCS.

Commenting for VHIO Communications, VHIO’s Cristina Saura, Principal Investigator of our Breast Cancer Group, who co-authored the latter study said, “While we still need to wait a while for these two novel treatment approaches to be approved, a number of patients at Vall d’Hebron have already benefited by participating in clinical trials carried out at our Breast Cancer Unit.”

She continued, “It is thanks to our dedication to developing the most promising drugs in the field and both leading and collaborating in these clinical trials that we can effectively combine our leading research with routine clinical care. We can consequently offer certain patients who are refractory to standard-of-care regiments, promising alternatives that are already in the treatment pipeline.”

Both HER2CLIMB and DESTINY-Breast01 shine a light on VHIO’s participation in multicenter and international studies that are driving advances against metastatic disease. They are also reflective of our dedication to cross border collaborations and promotion of translational science and clinical research of excellence.

Concerning the first of these phase IIs, HER2CLIMB -led by Rashmi Murthy at the MD Anderson Cancer Center, Houston (Texas-USA) and sponsored by Seattle Genetics- also counted on the expertise Mafalda Oliveira, Medical Oncologist and Clinical Investigator at VHIO’s Breast Cancer Group. 

“This trial sought to verify the efficacy of the triplet combination of tucatinib, trastuzumab and capecitabine in treating  patients with metastatic HER2+ breast cancer whose disease had progressed after pertuzumab and T-DM1, two previously approved agents that target HER2,” observed  Mafalda Oliveira, co-author of this present study.

The aim was to validate the performance of tucatinib, a new HER2 selective tyrosine kinase inhibitor, combined with the trastuzumab antibody and capecitabine, a chemotherapy agent used to treat breast cancer.

Results show that this triplet can significantly increase disease-free survival as well as overall patient survival. After one year of treatment, the percentage of those patients who were identified as progression-free totaled at 33% compared to 12% in the control group. Furthermore, this novel combination almost doubled two-year survival rates from 27% in the control group to 45% in patients receiving the triplet.

As importantly, the patients with brain metastases, who are largely excluded from the majority of clinical trials and also have very few treatment options available, also benefited from this approach. After one year, 25% of those treated with the combination remained progression-free, compared with 0% in the control group.

‘These result show great promise. Not only do they point to a new standard of care in the treatment of this cancer subtype but also provide hope for those patients who have gone on to develop  brain metastases; accounting for almost half of all this patient population,’  added Mafalda.

Results from the Daiichi Sankyo-sponsored DESTINY-Breast01 study, directed by Shanu Modi, Memorial Sloan Kettering Cancer Center – MSKCC (New York-USA), were presented at the very same General Session during the Symposium.

Co-authored by VHIO’s Cristina Saura, Principal Investigator of our Breast Cancer Group, also in collaboration with Javier Cortés, Translational Investigator of the same group and Head of Breast Cancer at the IOB Institute of Oncology (Quirónsalud Group in Madrid and Barcelona), this study built on findings from the phase I safety results of this second generation antibody drug conjugate; trastuzumab deruxtecan against advanced HER2- positive breast cancer previously treated with trastuzumab emtansine, published earlier this year in The Lancet Oncology***.

“This phase II study analyzed patient gains from this new generation of antibody drug conjugate; the first of which revolutionized the treatment of this tumor subtype. On the strength of our present results, we fully expect that our second generation contender will continue to do so,” said Cristina Saura.

Findings showed that 60.9% of those patients treated with this novel therapy had an objective response, with progression free survival at more than 16 months. These results are particularly important considering that these patients had progressed after an average of 6 other previous lines of therapy.

She concluded, “Results indicate that trastuzumab deruxtecan achieves lasting results showing important anti-cancer activity. As such, it could provide fresh hope for those patients with refractory disease who have limited treatment options.”

###

References:

 

*Tucatinib, Trastuzumab, and Capecitabine for HER2-Positive Metastatic Breast Cancer. Rashmi K. Murthy, Sherene Loi, Alicia Okines, Elisavet Paplomata, Erika Hamilton,  Sara A. Hurvitz, Nancy U. Lin, Virginia Borges, M.D., Vandana Abramson, M.D., Carey Anders, M.D., Philippe L. Bedard, M.D., Mafalda Oliveira, M.D., et al. December 11, 2019. DOI: 10.1056/NEJMoa1914609

Trastuzumab Deruxtecan in Previously Treated HER2-Positive Breast Cancer, Shanu Modi, Cristina Saura, Toshinari Yamashita, Yeon Hee Park, Sung-Bae Kim, Kenji Tamura, Fabrice Andre, Hiroji Iwata, Yoshinori Ito, Junji Tsurutani, M.D., Joohyuk Sohn, Neelima Denduluri,  et al. for the DESTINY-Breast01 Investigators. December 11, 2019. DOI: 10.1056/NEJMoa1914510

**Session GS1 – GS1. General Session 1

GS1-01 . Tucatinib vs placebo, both combined with capecitabine and trastuzumab, for patients with pretreated HER2-positive metastatic breast cancer with and without brain metastases (HER2CLIMB)

 December 11, 2019, 8:45 AM – 9:00 AM  Hall 3

https://www.abstractsonline.com/pp8/#!/7946/presentation/2037

Session GS1 – GS1. General Session 1

GS1-03. [Fam-] trastuzumab deruxtecan (T-DXd; DS-8201a) in subjects with HER2-positive metastatic breast cancer previously treated with T-DM1: A phase 2, multicenter, open-label study (DESTINY-Breast01)

 December 11, 2019, 9:15 AM – 9:30 AM  Hall 3

https://www.abstractsonline.com/pp8/#!/7946/presentation/2039

*** Tamura K, Tsurutani J, Takahashi S, Iwata H, Krop IE, Redfern C, Sagara Y, Doi T, Park H, Murthy RK, Redman RA, Jikoh T12, Lee C, Sugihara M, Shahidi J, Yver A, Modi S. Trastuzumab deruxtecan (DS-8201a) in patients with advanced HER2- positive breast cancer previously treated with trastuzumab emtansine: a dose-expansion, phase 1 study. Lancet Oncol. 2019 Jun;20(6):816-826. doi: 10.1016/S1470-2045(19)30097-X. Epub 2019 Apr 29.