Triple Positive Breast Cancer 2020

Berzeugende Daten Zu Sacituzumab

Auf dem Gebiet der Antikörper-Wirkstoff-Konjugate sind bei HER2-positiven Patientinnen in der Vergangenheit bereits deutliche Therapieerfolge erzielt worden35,36,37. Für Patientinnen mit triple-negativen und in Zukunft ggf. auch anderen Subtypen ist nun ein epitheliales Glykoprotein identifiziert worden, welches von Mammakarzinomzellen exprimiert wird und mit einer schlechteren Prognose verbunden ist38,39. Das ADC Sacituzumab-Govitecan ist gegen dieses Zielmolekül gerichtet und hat SN-38 als Payload, ein dem Irinotecan ähnliches, aber sehr potentes Zytostatikum. In den USA wurde Sacituzumab-Govitecan bereits auf Basis der guten Daten der frühen Therapiestudie zugelassen40.

ASCENT ist nun die randomisierte Phase-III-Studie, in der Patientinnen mit einem TNBC und mit 2 vorangegangenen Chemotherapien entweder mit Sacituzumab-Govitecan oder mit einer Chemotherapie nach Wahl der betreuenden Ärztinnen und Ärzte behandelt wurden60. Insgesamt waren 529 Patientinnen eingeschlossen worden. Die Studie wurde aufgrund eines deutlichen Unterschieds zwischen den Behandlungsarmen frühzeitig abgebrochen.

In der Patientinnenpopulation hatten alle Patientinnen zuvor ein Taxan erhalten, ca. 78% einen PARP-Inhibitor und ca. 2629% einen PD1/PD-L1-Inhibitor.

Metastatic Breast Cancer News From Asco 2020

Every year, oncology professionals and patient advocates gather in Chicago to hear the latest in cancer research at the American Society of Clinical Oncologys annual meeting .

ASCO 2020 was held in late May as a virtual program due to COVID-19. See below for a carefully selected list of findings presented by metastatic breast cancer experts.

All Metastatic Breast Cancer

• Early Local Therapy Did Not Extend Survival in Patients With Newly Diagnosed Metastatic Breast Cancer The ASCO Post reports on a study that found removing the primary tumor with surgery or radiation therapy did not lead to longer survival in people whose first breast cancer diagnosis was stage 4 .
• ASCO: How I Will Change My Practice for My Breast Cancer Patients Oncologist Dr. Kirshner discusses four studies presented at ASCO that he believes to be practice-changing. The first trial applies only to people with early-stage triple negative breast cancer. The rest of the content is for people with metastatic disease

Hormone Receptor Positive Metastatic Breast Cancer

What Is Triple Negative Breast Cancer 12

Triple-negative breast cancer is a cancer that tests negative for progesterone and estrogen receptors, and excess HER2 protein. This means that the growth of the cancer is not fuelled by the estrogen and progesterone hormones, or by the HER2 protein. So, TNBC does not respond to hormonal therapy medicines or medicines that target HER2 protein receptors.

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Cancer Alters Your Life And It Never Really Leaves You

For those beginning their cancer journey, Carol has two bits of advice. “Definitely don’t put off getting anything suspicious checked.” She doubts she would have found the cancer early if she weren’t seeing Dr. Khoo regularly. “Lastly, know that cancer never leaves you. Post-cancer PTSD and anxiety is real, even after treatment ends, and that’s OK.”

Because El Camino Health knows that the emotional toll may continue long after cancer treatment ends, they’ve developed the Survivorship Program to support patients like Carol who may have questions or fears about what’s happening with their mind, body or emotions.

Now at age 33, Carol’s life is basically back to normal, although she still struggles with the possibility that she may not be able to have more children through natural means.

“As much as cancer sucked,” states Carol, “I truly appreciate the many new perspectives it gave me: A glimpse of the lives of the doctors and nurses providing care. The depths of empathy of everyone on a cancer journey. And it forced me to jump off the never-ending achievement treadmill with no regrets. Life is such a gift!”

Clinicopathological Characteristics Of Patients

Among 491,913 patients originally identified from SEER database, cases of 33,339 TP-FBCs and 336 TP-MBCs from 2010 to 2017 were included in our study. According to the percentage of TP-FBC/TP-MBC to total FBC/MBC at each year , we firstly showed the trends of the subsets in 8 years . Generally, the subtype of TPBC was more prevalent in males than that in females with the exception of 2012.

Fig. 1

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What Are The Newest Triple Negative Breast Cancer Medicines

Several medicines have been approved or are under clinical trial for the treatment of TNBC.

Here are some of them:

Keytruda 4

Keytruda is used for the treatment of advanced melanoma, metastatic nonsquamous NSCLC, recurrent or metastatic Head and Neck Squamous Cell Carcinoma , recurrent classical Hodgkin Lymphoma , locally advanced or metastatic urothelial carcinoma, solid tumours having the biomarkers MSI-H or dMMR, recurrent locally advanced or metastatic gastric or gastroesophageal junction adenocarcinoma, triple-negative breast cancer.

On November 13, 2020, the Food and Drug Administration granted accelerated approval of Keytruda in combination with chemotherapy for the treatment of people with locally recurrent or metastatic triple-negative breast cancer whose tumors express the PD-L1 biomarker, based on improved clinical outcomes.

Tecentriq 5

Tecentriq is used for the treatment of locally advanced or metastatic urothelial carcinoma, and for the treatment of metastatic non-small cell lung cancer . Tecentriq in combination with nab-paclitaxel is currently approved in more than 70 countries worldwide, including the US and across Europe, for the treatment of adults with unresectable locally advanced or metastatic TNBC in people whose tumours express.

On August 2019, the European Medicines Agency approved Tecentriq in combination with braxane for people with PD-L1-positive, metastatic triple-negative breast cancer.

Trodelvy 6,7

Talzenna 8

Lynparza 9,10

How Can I Access A New Her2 Positive Breast Cancer Medicine

If youve received a triple negative breast cancer prognosis and are trying to access a medicine that is approved outside of your country of residence, we might be able to help you access it with the help of your treating doctor. You can read more about the medicines we can help you access and their prices below:

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Immune Checkpoints And Immunotherapy Trials In Hr+ Breast Cancer

Despite the limited number of TILs, low PD-L1 expression and low mutational burden in HR+ breast cancer , there has been an effort to determine if ICB has a role in HR+ disease . While, to date, clinical trials testing ICB in HR+ breast cancer have not yet translated to FDA approval, there is opportunity to learn from both past and ongoing trials to identify the ideal therapeutic sequencing, combination strategies and patient population to extract value in this immunologically cold subtype of breast cancer, as reviewed below.

Table 2 Clinical trials in HR+ breast cancer assessing the safety and efficacy of ICB as monotherapy or in combination with chemotherapy and other treatment modalities.

What Are The Symptoms Of Her2

Its not possible to self-determine whether you have HER2-positive breast cancer. If your doctor suspects cancer, further testing will reveal whether you are HER2-positive.

Overall, its important to see your doctor right away if you notice any of the following symptoms:

• any new or changing lumps in your breast or armpit areas
• clear, colored, or bloody nipple discharge
• unexplained pain in your breasts
• changes in your nipples or breast skin, such as dimpling, reddening, or scaliness
• nipples that turn inward

Hormone treatments may be an option for cancer thats also HR-positive.

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Patient Cohorts And Clinicopathologic Features

A total of 446 breast cancer patients undergoing neoadjuvant chemotherapy were included, as shown in Fig. . Table shows main clinicopathologic features of the overall cohort. The majority of patients had tumors of ductal histology and poor differentiation on baseline biopsy and almost 94% of patients had clinical stage IIIII breast cancer . Tumor phenotypes on baseline biopsy were distributed as follows: HR-positive/HER2-negative 23.5% , triple-negative 35% and HER2-positive 41.5% . In the great majority of cases patients underwent anthracycline-taxane-based neoadjuvant chemotherapy and among HER2-positive patients, 86.5% received anti-HER2 blockade associated with neoadjuvant chemotherapy . One-hundred fifty-five patients achieved pCR after neoadjuvant chemotherapy . The distribution of pCR rates according to tumor phenotype is shown in Table . As expected, significantly higher rates of pCR were observed in triple-negative and HER2-positive subgroup as compared to HR-positive/HER2-negative subtype . Among 291 patients with residual disease after neoadjuvant therapy, the distribution of breast cancer phenotype was: HR-positive/HER2-negative 35.7% , triple-negative 32% and HER2-positive 32.3% . 17.9% of patients received further chemotherapy in the adjuvant setting among HER2-positive breast cancer patients, more than 90% received adjuvant anti-HER2 therapy 227 patients received adjuvant hormonal therapy.

Fig. 1: Flow diagram of the study.

Immunotherapies Impassion131 Impassion130 Keynote

The PD-L1 inhibitor atezolizumab has now been authorised for patients with advanced triple-negative breast cancer following the findings of the IMpassion130 trial, which revealed an improvement in progression-free survival and overall survival in patients with immune cell PD-L1-positive tumours30,31. Similarly, the KEYNOTE-355 study showed that the addition of pembrolizumab to chemotherapy significantly improved progression-free survival. In the USA, pembrolizumab has already been authorised for this indication.

The IMpassion130 study selected nab-paclitaxel as combination therapy for atezolizumab. Various chemotherapies were permitted in the KEYNOTE-355 study. Based on a subgroup analysis of combination partners, the KEYNOTE-355 study found no differences between the chemotherapy options with which pembrolizumab was combined.

The IMpassion131 study32investigated a study population similar to that of IMpassion130, but whose subjects were randomised to paclitaxel + atezolizumab or to paclitaxel monotherapy at a 2:1 ratio32. A total of 651 patients were recruited, of which 292 had tested positive for PD-L1 . Neither in the PD-L1-positive population nor in the overall population was a benefit observed for progression-free survival or overall survival32.

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Overall Survival Analysis Of The Solar

The PI3K inhibitor alpelisib was recently approved after it had been shown to improve median progression-free survival from 5.7 months to 11 months in patients with HER2/HR+ metastatic breast cancer and with a somaticPIK3CAmutation who had previously received endocrine therapy 41. Data on overall survival have now been reported revealing 181 patients died 42.

Even if the addition of alpelisib to fulvestrant improved overall survival from 31.4 months to 39.3 months , this difference was not statistically significant . A subgroup analysis suggested that a significant part of the effect was attributable to patients with a lung or liver metastasis. In this subgroup of 190 patients, the difference in median overall survival was almost 15 months 42.

As testing is one of the prerequisites for alpelisib therapy, testing and methodology are increasingly a focus of interest. Mutations can be analysed from DNA extracted from paraffin-embedded tumours as well as from circulating DNA . According to its protocol41, the SOLAR-1 study tested for the following mutations: C420R, E542K, E545A, E545D , E545G, E545K, Q546E, Q546R, H1047L, H1047R and H1047Y. Alpelisib is likely to be effective against tumours with a number of other different mutations, but prospective data on this should be awaited. It should be noted, however, that mutations other than those mentioned are very rare, as the vast majority of mutations in PIK3CA are restricted to three so-called hotspots.

Icb In Combination With Chemotherapy For Hr+ Breast Cancer

Given the promising results using chemotherapy with ICB in TNBC, there has been an effort to replicate similar strategies in HR+ breast cancer. Like the early monotherapy trials, the initial chemotherapy plus ICB combination trials focused on heavily pretreated patients in the metastatic setting. The first of these trials used eribulin as a combination agent. Eribulin is a microtubule inhibitor that, in addition to antimitotic activity, has been shown to reverse epithelial-mesenchymal-transition and decreased numbers of FOXP3 and PD-L1 expression as measured through IHC . In the phase II trial, eribulin with or without pembrolizumab was evaluated in 88 patients with HR+/HER2- metastatic breast cancer . In this cohort, the patients had received at least two prior lines of endocrine therapy and up to two lines of chemotherapy. The addition of pembrolizumab to eribulin did not add any benefit to median PFS . In addition, PD-L1 status, TILs and TMB were not associated with median PFS. Importantly, 54.6% of patients who received E+P experienced grade 3-4 adverse events, including 2 treatment related deaths.

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Clinical Features And Treatment

The study included 85 patients with a median age of 47 years at the time of diagnosis . The mean clinical tumor size at presentation was 3 cm , with 83.5% of patients having at least clinical T2 tumors. Four patients presented with inflammatory carcinoma. Fifty patients were clinically node-positive and/or had biopsy-proven nodal metastasis before chemotherapy. Most patients received AC-THP as the neoadjuvant regimen. Fifty-two patients underwent mastectomy and 33 had breast-conserving surgery.

Clinical and Histomorphologic Features of Studied Patients and Hormone Receptor and HER2 Results Determined in Pretreatment Core Biopsies

What Are The Types Of Triple Negative Breast Cancer Treatments Available12

There are several triple negative breast cancer treatments available. The patients treating physician might opt for a combination of surgery, radiation, and chemotherapy.

• Mastectomy: the surgeon removes the breast and nearby lymph nodes to see if the cancer has spread.
• Lumpectomy: the surgeon removes the lump from the breast. He or she also removes nearby lymph nodes to see if the cancer has spread.
• Radiation: Lumpectomies are usually followed by radiation therapy to kill any remaining cancer cells.
• Chemotherapy: The goal of chemotherapy is to kill cancerous lumps that may have spread elsewhere in the body.

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Early Detection And Treatment Research

The Breast Specialized Programs of Research Excellence are designed to quickly move basic scientific findings into clinical settings. The Breast SPOREs support the development of new therapies and technologies, and studies to better understand tumor resistance, diagnosis, prognosis, screening, prevention, and treatment of breast cancer.

The NCI Cancer Intervention and Surveillance Modeling Network focuses on using modeling to improve our understanding of how prevention, early detection, screening, and treatment affect breast cancer outcomes.

The Confluence Project, from NCI’s Division of Cancer Epidemiology and Genetics, will develop a research resource that includes data from thousands of breast cancer patients and controls of different races and ethnicities. This resource will be used to identify genes that are associated with breast cancer risk, prognosis, subtypes, response to treatment, and second breast cancers.

The goal of the Breast Cancer Surveillance Consortium , an NCI-funded program launched in 1994, is to enhance the understanding of breast cancer screening practices in the United States and their impact on the breast cancer’s stage at diagnosis, survival rates, and mortality.

Where Do These Numbers Come From

The American Cancer Society relies on information from the Surveillance, Epidemiology, and End Results database, maintained by the National Cancer Institute , to provide survival statistics for different types of cancer.

The SEER database tracks 5-year relative survival rates for breast cancer in the United States, based on how far the cancer has spread. The SEER database, however, does not group cancers by AJCC TNM stages . Instead, it groups cancers into localized, regional, and distant stages:

• Localized: There is no sign that the cancer has spread outside of the breast.
• Regional: The cancer has spread outside the breast to nearby structures or lymph nodes.
• Distant: The cancer has spread to distant parts of the body such as the lungs, liver or bones.

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Icb Monotherapy In Hr+ Breast Cancer

In the phase 1b JAVELIN trial, 168 heavily pretreated patients with metastatic breast cancer, regardless of subtype or PD-L1 status, were treated with the PD-L1 inhibitor, avelumab . Of the 168 patients, 72 had HR+/HER2- disease and the ORR for this group was 2.8% compared to 5.2% in the TNBC group. The median duration of response was not reached. In addition, subgroup analysis by PD-L1 status did not reveal any trend in efficacy. Given the low ORR, avelumab was determined to have limited therapeutic benefit as monotherapy in patients with metastatic HR+/HER2- breast cancer. Altogether, the KEYNOTE-028 and JAVELIN trials revealed the limited single-agent efficacy of ICB in HR+ breast cancer, particularly in heavily pretreated disease. The limited response to ICB monotherapy led to the inclusion of chemotherapy and other systemic therapeutics that may have synergism with ICB, a strategy used in TNBC.

High Tumor Responses With Trastuzumab Deruxtecan

The DESTINY-Breast01 trial was not a randomized study, so all patients in the trial received trastuzumab deruxtecan.

Nearly all of the more than 180 women in the trial had at least some reduction in the size of their tumors, with 61% experiencing substantial reductions, Dr. Krop reported. Several patients had no evidence of cancer following treatment, known as a complete response. The median progression-free survival was more than 16 months.

Dr. Krop called the results compelling, noting that the tumor response rate is roughly double or triple what we typically see in other studies of this third- or later-line population.

Most of the treatment-related side effects seen in the trial were mild, Dr. Krop said. Even so, 15% of the participants stopped taking the drug because of side effects. Nearly all of these women were those who experienced ILD. Four of the women who developed ILD died as a result.

Why we have this particular risk is unclear, he said. And clearly we need to do more research to identify those patients who are at risk of getting the most severe cases of ILD and how to mitigate the risk.

For future studies of the drug, Dr. Krop said, clinicians will be advised to carefully monitor patients for any evidence or symptoms of ILD and, if they suspect it has developed, to immediately stop the drug and treat the patient with steroids.

We definitely have to be cautious, he continued. But I dont think is a major barrier to moving this drug forward.

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