Updates From the 2016 ASCO Annual Meeting

Read about the latest in research findings presented at this year’s American Society of Clinical Oncology meeting
Breast Cancer News
June 5, 2016
Nicole Katze, MA

Each year, oncologists, cancer researchers and patient advocates attend the American Society of Clinical Oncology (ASCO) Annual Meeting to hear the latest updates in research and cancer care. Living Beyond Breast Cancer staff are in Chicago to cover this year's meeting, which takes place from June 3-7.

Below, our editor and manager of content development, Nicole Katze, MA, updates you on interesting breast cancer findings presented at this year's meeting.

Highlights From Saturday, June 4

After presentations on three studies of chemotherapy regimens, Tiffany A. Traina, MD, of Memorial Sloan Kettering Cancer Center, summarized the afternoon’s sessions in three “contemporary questions of our time.”

  • Are we undertreating?
  • Are we overtreating?
  • Is there a better way to give chemotherapy medicines we already know work well?

Are We Undertreating?
Dr. Traina pointed to the FinXX trial, presented by Heikki Joensuu, MD, to answer the question of undertreatment. FinXX looked at adding capecitabineinfo-icon (Xelodainfo-icon) to common anthracyclineinfo-icon plus taxaneinfo-icon chemotherapy treatment for early-stage breast cancerinfo-icon. Dr. Joensuu presented the study’s 10-year follow-up results.

We already know capecitabine works well for some people with metastaticinfo-icon breast cancer. But so far, there hasn’t been much evidence to use it in early-stageinfo-icon disease. After 10 years, FinXX confirmed what other studies have also found: that adding capecitabine to anthracycline plus taxane chemotherapy doesn’t lead to better survival. In Dr. Traina’s remarks, she noted this means “more chemotherapy is not the answer.”

So in this case, the answer to "Are we undertreating when we give less chemotherapy?" is "no."

Despite the negative findings, a subanalysis of FinXX showed that in people with triple-negative breast cancerinfo-icon, adding capecitabine seemed to improve outcomes.

Are We Overtreating?
Joanne L. Blum, MD presented the findings of the “ABC trials,” three separate trials brought together for final analysis. These trials were:

  • USOR 06-090
  • NSABP B46-I
  • NSABP B-49

The three trials explored whether disease-free survival improved when breast cancer was treated with two chemotherapy medicines – docetaxelinfo-icon (Taxotereinfo-icon) plus cyclophosphamideinfo-icon (Cytoxaninfo-icon), a regimeninfo-icon known as TC – compared to treatment with three chemotherapy medicines – a taxane, an anthracycline and cyclophosphamide, known as TaxAC.

More than 4,000 people with HER2-negative disease participated across the three trials, and in the end, the studies found that the TaxAC regimens are a good standard of careinfo-icon. The TC regimen was not better than TaxAC.

So in this case, the answer to "Are we overtreating when we give three chemotherapy medicines?" is "no."

Dr. Blum did note that while more research is needed, the number of lymphinfo-icon nodes positive for cancer cells seemed to impact how well TaxAC worked overall.

Is there a better way to give chemotherapy medicines we already know work well?
According to Dr. Traina, the PANTHER study, presented by Jonas C. S. Bergh, MD, PhD, gives some reason for researchers to rethink how chemotherapy doses and schedules are determined.

PANTHER tested whether chemotherapy could be given with doseinfo-icon density – meaning there's less time between each chemotherapy treatment than in a standard regimen – based on white blood cellinfo-icon counts of the person receiving it. They compared the recurrenceinfo-icon-free survival of this method to that of the usual every-3-weeks schedule.

Overall, the researchers were able to give more chemotherapy in the study arm than the standard arm. Yet the rate of recurrence-free survival didn’t change. Still, a secondary endpointinfo-icon, event-free survival, was statistically significantinfo-icon, meaning it didn’t happen randomly. This one finding is enough for the PANTHER trial to support dose-dense treatment.

A New Anticancer Medicineinfo-icon: Utidelone
A positive study was presented about utidelone, a newer anticancer medicine for metastatic breast cancer that has already been treated with taxanes and anthracyclines. The study compared utidelone plus capecitabine to capcitabine alone.

The results showed improvement in progression-free survivalinfo-icon. And very early results suggest a significant improvement in overall survival. The researchers believe these promising results could mean utidelone might one day be a better option than ixabepiloneinfo-icon (Ixempra), another medicine in the same class.

Though this study shows some promise for utidelone, Steven J. Isakoff, MD, PhD noted in his discussion of these abstracts that there are some obstacles to the clinicalinfo-icon use of this medicine. He mentioned that utidelone requires daily IV treatment, has a high rate of neuropathyinfo-icon, and that other, very similar medicines are already FDAinfo-icon approved.

At the close of Saturday’s presentations, Elizabeth Ann Mittendorf, MD, PhD commended the researchers on the ACOSOG Z0011 trial, the 10-year follow up of which was presented by Armando E. Giuliano, MD, FACS. Z0011 compared outcomes for people with node-negativeinfo-icon breast cancer who had axillary lymph node dissectioninfo-icon (ALND) versus sentinel lymph nodeinfo-icon dissection (SLND).

The study found that there was no difference between the two for local recurrence, regionalinfo-icon recurrence, disease-free survival or overall survival. This suggests that more people can have the less invasive SLND procedure, which Dr. Mittendorf calls practice-changing.

Highlights From Sunday, June 5

Sunday, ASCO featured posters and poster discussions on a wide variety of topics related to breast cancer. Here are some notable themes:

Extending Letrozoleinfo-icon ... Or Not

During the plenary session, experts discussed the top four abstracts submitted across all cancer types, as chosen by ASCO. One was a late-breaking abstract on MA.17R, a randomized trial on the use of letrozole (Femarainfo-icon) in postmenopausalinfo-icon women with early-stage breast cancerinfo-icon.

MA.17R explored whether letrozole should be given for 5 years or extended to 10 years, much like the ATLAS study reported for tamoxifen in 2012. In this study, one group of women took letrozole for 5 years plus 5 years of a placeboinfo-icon pill; the other group took letrozole for 10 years.

Study author Paul E. Goss, MD, PhD presented the findings, which seemed to support extending letrozole treatment from 5 years to 10 years. He reported one-third fewer recurrences overall among those who took letrozole for 10 years. Dr. Goss noted a significantly lower chance of breast cancer returning in the healthy (called contralateralinfo-icon) breast. Side effects for 10 years of treatment were roughly the same as those seen in women taking letrozole for 5 years.

But discussant Ian E. Smith, MD said extending letrozole to 10 years isn’t supported. Most of the data that impacts whether the results are statistically significantinfo-icon – unlikely to happen by chance – came from the risk of breast cancer developing in the opposite breast. That measure isn’t typically used to decide if a treatment is successful, he said. At the same time, two endpoints that are typically used, distant recurrenceinfo-icon and overall survival, showed little or no difference when letrozole was given for 5 or 10 years.

In a later townhall-style discussion, experts agreed a small group would have improved survival with extended letrozole, but this group is too small for 10 years of letrozole to become standard treatment.

Neratinib in Breast Cancers With HER2 Mutations

Alexandra Thomas, MD, FACP of the University of Iowa discussed a phase II trialinfo-icon of neratinib submitted by Cynthia X. Ma, MD, PhD, et al. The study looked at the use of neratinib, a tyrosine kinase inhibitor, in metastaticinfo-icon breast cancers that had HER2 mutations, but not amplification, or too much HER2. Past early studies showed neratinib may stop growth in cells with HER2 mutations.

This study found that neratinib was effective in tumors that had been heavily treated in the past with other anticancer medicines. Most of the tumors were hormone receptorinfo-icon-positive. That suggests neratinib should be paired with a hormonal therapyinfo-icon such as fulvestrantinfo-icon (Faslodexinfo-icon), the authors said. Dr. Thomas noted that similar research was presented at the 2015 San Antonio Breast Cancer Symposium and an update could take place at this year’s meeting. 

Premenopausalinfo-icon Women

In a subset analysisinfo-icon of the PALOMA-3 trial, Sibylle Loibl, MD, PhD, et al, found that palbociclib (Ibrance) plus fulvestrant shows promise in treating hormone receptor-positive metastatic breast cancer in pre- and perimenopausalinfo-icon women. Participants received these medicines along with goserelininfo-icon (Zoladex) to suppress the ovaries. Adding palbociclib did not further affect ovarianinfo-icon function.

Though this was a subset analysis, it shows a need to continue researching this combination for younger women. Because there are limited data and current treatment options are limited for premenopausal women, this treatment combination is of special interest, said poster discussant Cornelia Liedtke, MD, PhD

Highlights from Monday, June 6

The Cancer Moonshot Initiative

On Monday, Vice President Joe Biden spoke to ASCO conference attendees in a special address about the National Cancer Moonshot Initiative, the White House’s plan to tackle cancer. President Obama announced the Moonshot Initiative in January, placing Vice President Biden in charge.

According to ASCO president Julie M. Vose, MD, MBA, FASCO, who introduced the vice president, the Initiative strives to break down barriers, share information and promote research.

In his speech, Vice President Biden urged the medical community to support the White House and the Moonshot Initiative.

“There’s never been a major undertaking I’ve been assigned where I haven’t known at least as much or more than the people advising me,” he said. “Except here. That’s why I need you.”

Biden described the magnitude of the work ahead by stressing that “no single oncologistinfo-icon or cancer researcher can find the answer on his or her own.”

Cancer researchers need to change their mindset: more openness, in collaboration and in data sharing, as well as open-mindedness, the vice president said. Mid-speech, he acknowledged organizations currently building data aggregation sites, and asked them to imagine a world where they worked together.

“You’re spending hundreds of millions of dollars,” he said. “Imagine if it were coordinated.”

Biden called for more “team science,” research that spans disciplines and skillsets. He seeks a streamlined approach to clinicalinfo-icon trials that offers easier access. And he announced the Genomic Data Commons, a database that allows anyone to view and compare genomic data from clinical trials. From this point forward, he said, all National Cancer Instituteinfo-icon-sponsored clinical trials will be required to include their data through the Commons. He assured attendees that the database was built to keep genomic data safe and secure.

Later this month the first official National Cancer Moonshot Summit will be held at the White House and simultaneously in 75 other locations. Individuals and organizations can join the summit online or host one in their community. To learn more, visit whitehouse.gov/cancermoonshot.

Neoadjuvant Therapyinfo-icon

Three studies of neoadjuvant, or pre-surgeryinfo-icon, therapyinfo-icon were presented on Monday, discussed by Stephen K. L. Chia, MD, FRCPC.

The first, KRISTINE, compared the pre-surgery use of T-DM1 (Kadcyla) plus pertuzumabinfo-icon (Perjeta) to the pre-surgery use of docetaxelinfo-icon (Taxotereinfo-icon) plus carboplatininfo-icon (Paraplatininfo-icon) plus trastuzumabinfo-icon (Herceptininfo-icon) plus pertuzumab, a combination called TCHP, in HER2-positive, early-stage breast cancerinfo-icon. This study was presented by Sarah A. Hurvitz, MD.

The goal was to look for pathologic complete responseinfo-icon (pCR), which means having no cancer cells present in the breast or lymphinfo-icon nodes at the time of surgery. Typically, reaching pCR means the cancer is less likely to grow or spread.

The study found neoadjuvant TCHP prompted a higher rate of pCR than neoadjuvant T-DM1 plus pertuzumab. Still, some of the data pointed to fewer side effects with the T-DM1/pertuzumab combination. Dr. Chia noted that this trial, along with NeoSphere, TRYPHAENA and I-SPY 2, all support the use of neoadjuvant pertuzumab with a taxaneinfo-icon chemotherapyinfo-icon

The second study, NSABP B-41, was presented by André Robidoux, MD, FRCSC, and also focused on HER2-positive early-stage breast cancer. A 5-year outcomes report, B-41 compared:

The three combinations worked equally well in protecting participants from a cancer recurrenceinfo-icon and from death, but those within each group acheived pCR tended to do better — especially those whose disease was not estrogen receptor-positiveinfo-icon.

In the final neoadjuvant presentation, Luca Gianni, MD, spoke about the ETNA study. ETNA was a phase III trialinfo-icon that compared neoadjuvant nab-paclitaxel (Abraxaneinfo-icon) to paclitaxel, both followed by an anthracyclineinfo-icon for HER2-negative breast cancer at high risk for return. The researchers compared the pCR rates for the two combinations and found no statistically significantinfo-icon difference between the two. But a smaller subset analysisinfo-icon did find that triple-negative breast cancerinfo-icon was more likely to achieve pCR with nab-paclitaxel.

A Biosimilar for Herceptin?

Hope Rugo, MD, presented the findings of the HERITAGE phase III trial, which compared trastuzumab to its proposed biosimilar, MYL-1401O. Biosimilars are medicines that mimic biological medicines, by being very similar to, although not exactly the same as, the original biological medicineinfo-icon. They are often less expensive than the original medicine, expanding access to the treatment to lower-income people and countries.

To be FDAinfo-icon approved as an alternative to the original medicine, clinical trials must find no meaningful difference between the biosimilar and the original medicine – the biosimilar should treat the cancer as well and have the same or similar side effects.

HERITAGE randomly assigned participants to trastuzumab plus a taxane chemotherapy or to MYL-1401O plus a taxane chemotherapy. The response rateinfo-icon was measured at 24 weeks. The research team determined that the overall response rate, as well as early progression-free survivalinfo-icon, were the same for both medicines. The side effects were also equal, and most likely caused by the taxane. This means MYL-1401O may be on its way to becoming an appropriate biosimilar for trastuzumab.

Hormonal Therapyinfo-icon

Three trials of different hormonal therapy options were presented Monday, with Nancy E. Davidson, MD, serving as the discussant. Tasked with taking the audience through the “marathon” of hormonal therapy, Dr. Davidson described how these three trials fit into the bigger picture of current and future hormonal therapy use.

Dr. Davidson suggested four important ways for oncologists to think about hormonal therapy, in order to improve outcomes for people with breast cancer:

  • Lengthening the use of hormonal therapy
  • Combining new medicines or methods with standard treatment
  • Using tailored assessments of risk of recurrence to decide on treatment
  • Findings ways to improve people's ability to continue treatment over time and to access care

Early Breast Cancer Trialists' Collaborative Group (EBCTCG) data was presented by Hongchao Pan, PhD, on the long-term risk of recurrence after taking 5 years of hormonal therapy. This study, an analysis of data from 91 clinical trials, showed that even after 5 years of hormonal therapy, the risk of distant recurrenceinfo-icon continues through the next 15 years. Dr. Davidson mentioned that several other large trials have also supported the use of hormonal therapy beyond 5 years.

Next, Dr. Davidson approached the question of adding new medicines to standards of care. She pointed to the PALOMA-2 trial, which officially confirmed the findings of PALOMA-1. Looking at palbociclib (Ibrance) plus letrozoleinfo-icon (Femarainfo-icon) vs. placeboinfo-icon plus letrozole, the PALOMA trials show that palbociclib plus letrozole significantly improves progression-free survival in women with hormone receptorinfo-icon-positive metastaticinfo-icon breast cancer. The findings support studying palbociclib in early-stageinfo-icon disease. Dennis J. Slamon, MD, PhD, presented the PALOMA-2 findings.

Julie Lemieux, MD, MSc’s presentation of the quality-of-life findings for the MA.17R study that was presented at Sunday’s plenary session point to the need for tailored risk of recurrence assessments. That study, described in our Sunday, June 5th, coverage, found that extending letrozole to 10 years benefited a small number of women in the MA.17R trial. If doctors are able to pinpoint which people need certain medicines, Dr. Davidson suggested, these smaller but meaningful findings can be applied when needed. The quality-of-life assessment revealed no new side effects or issues regarding quality of lifeinfo-icon associated with longer use of letrozole compared to the standard use. These findings are important for discussions between doctors and people in treatment, because side effects and quality of life concerns should be considered in treatment decisions. 

Our expert, Julie Gralow, MD, will provide an overview of the meeting's findings during our free webinar, Breaking News: Updates from ASCO’s 2016 Annual Meeting, Friday, June 17 at noon ET.

To get live updates, follow LBBC on Facebook, Twitter and Instagram, and use #LBBContheBeat on each social network.

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