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New targeted therapy approved for early-stage HER2-positive breast cancer


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The KATHERINE trial looked at the benefit of the new drug, Kadcyla, for treating early-stage breast cancer after surgery and chemotherapy. The results of this study led to FDA approval in May 2019. (6/17/19)

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Contents

At a glance In-depth
Findings     Limitations                             
Clinical trials Resources and references
Questions for your doctor  


STUDY AT A GLANCE

This study is about:

whether Kadcyla (also called T-DM1) is beneficial for patients with early-stage HER2-positive breast cancer who still show signs of disease after surgery and initial postsurgery treatment.

Why is this study important?

Patients with HER2-positive breast cancer who have remaining disease after surgery have worse overall outcomes than patients with no evidence of cancer.

This is the first clinical study to show that a HER2 therapy can help these patients.

Study findings: 

All patients received neoadjuvant therapy with chemotherapy plus Herceptin. Patients with remaining disease were randomly assigned to receive Kadcyla or Herceptin. Each group had 743 patients.

  • Patients in the Kadcyla treatment group had a 50% lower risk of developing further invasive breast cancer or death than the women in the Herceptin group.
     
  • Researchers expect that more patients (88%) in the Kadcyla group than the Herceptin group (77%) will remain disease-free at 3 years after treatment.
     
  • Kadcyla was effective in patients who had either hormone receptor-positive or hormone receptor-negative cancers.
     
  • Kadcyla was effective in patients with or without cancer in their lymph nodes.

The most common adverse events included:

  • fatigue
  • nausea
  • liver problems
  • musculoskeletal pain
  • bleeding
  • low platelet levels
  • headache, weakness, numbness or pain in hands or feet
  • joint pain

What do the experts say?

Kadcyla was granted FDA approval on May 3, 2019 for use in patients with HER2-positive breast cancer with residual disease after chemotherapy and treatment with Herceptin.

What does this mean for me?

If you have early-stage HER2-positive breast cancer, Kadcyla may be a treatment option for you. Kadcycla is also approved for patients with Her2-positive, metastatic breast cancer.

Share your thoughts on this XRAYS article by taking our brief survey.

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IN-DEPTH REVIEW OF RESEARCH
Study background:

The long-term outlook is good for patients with early HER2-positive breast cancer who have no evidence of disease after neoadjuvant therapy. Patients who have residual disease, however, have a higher risk for recurrence and a worse overall outcome. Researchers have been exploring improved treatments for these patients.

Kadcyla (also known as ado-trastuzumab emtansine or T-DM1) combines the HER2-antibody trastuzumab (Herceptin) with the chemotherapy drug emtansine.

Kadcyla was approved for use for metastatic HER2-positive breast cancer in 2013. Researchers reasoned that it might also benefit women with early-stage HER2 cancers.

This is the first clinical trial to evaluate a HER-2 targeted therapy for higher-risk patients who had early-stage HER2-positive breast cancer with residual disease.

Researchers of this study wanted to know:

whether Kadcyla/T-DM1 benefits patients with early-stage HER2-positive breast cancer with remaining disease after surgery, and patients with initial post-surgery treatment (either at the primary site or in lymph nodes).

Study design:

The KATHERINE trial is a multi-center, phase III trial involving patients with HER2-positive, early-stage breast cancer with residual disease after surgery and post-operative chemotherapy and trastuzumab. The trial was sponsored by pharmaceutical manufacturers F. Hoffmann–La Roche and Genentech and conducted under FDA oversight.

  • Between April 2013 and December 2015, the trial enrolled 1,486 patients with HER2-positive breast cancer who were initially treated with HER2 inhibitors and chemotherapy and had residual disease after surgery.
  • Participants included women from 273 trial sites in 28 countries; 72% had hormone receptor-positive breast cancers.
  • The average age was 49 years in both treatment groups. Patients were 73% white, 9% Asian, 3% black and 6% American Indian or Alaskan Native; 10% were of multiple or unknown ancestry.
  • Patients were ineligible if they had considerable residual cancer after mastectomy or positive margins after breast-conserving surgery, cancer that grew during initial post-surgery therapy, or heart problems.

Patients were randomly assigned to the Kadcyla treatment group or Herceptin treatment group; each group included 743 patients. Treatment included either:

  • 3.6 mg of Kadcyla per kilogram (2.2 pounds) of body weight or
  • 6 mg of Herceptin per kilogram of body weight every 3 weeks for 14 cycles.

The primary end point was the length of time between enrollment and disease-free survival (defined as absence of breast cancer in either breast, local or distant recurrence or death from any cause).

Study findings: 

Patients in the Kadcyla treatment group had 50% lower risk of invasive breast cancer or death than the women in the Herceptin group.

  • Among the patients in the Kadcyla treatment group, 91 of 743 (12%) had invasive cancer or died.
  • Among the patients in the Herceptin treatment group, 165 of 743 (22%) had invasive cancer or died.
  • An estimated 88% of the Kadcyla group and 77% of the Herceptin group were projected to remain disease-free at 3 years.
  • Kadcyla was effective in patients with hormone receptor-positive or hormone receptor-negative cancers.
  • Kadcyla was effective in patients with or without cancer in their lymph nodes.

Some patients in both groups had a distant recurrence as the first cancer detected after the trial began:

  • just over 10% (78) in the Kadcyla group
  • just under 16% (118) in the Herceptin group

The safety data for Kadcyla in this clinical trial was similar to prior safety trials. Patients in the Kadcyla group experienced more adverse events than patients in the Herceptin group.

  • 98 deaths were reported during the trial:
    • 42 patients in the Kadcyla group
    • 56 patients in the Herceptin group
       
  • 133 patients discontinued Kadcyla; of these, 77 switched to Herceptin only.
     
  • Adverse events of any grade were common in both groups (99% in the Kadcyla group and 93% in the Herceptin group). The most common adverse events included:
    • fatigue
    • nausea
    • liver problems
    • musculoskeletal pain
    • bleeding
    • low platelet levels
    • headache, weakness, numbness or pain in hands or feet
    • joint pain
       
  • Serious adverse events occurred in 26% of the Kadcyla group. The most common were:
    • decreased platelet levels in 6% of patients
    • hypertension in 2% of patients
       
  • Serious adverse events occurred in 15% of Herceptin group. The most common were:
    • radiation-related skin injury in 1% of patients
    • hypertension in 1% of patients

Kadcyla was granted FDA approval on May 3, 2019 for patients with HER2-positive breast cancer with residual disease after chemotherapy and Herceptin treatment.

Limitations:

  • Kadcyla is only useful for people with HER2-positive breast cancer. FDA approval required testing with an approved diagnostic test to determine whether the person's breast cancer is HER2-positive.
  • It is unknown whether tumors that are originally HER2-positive but become HER-negative during treatment may respond to Kadcyla.

Conclusions:

Kadcyla has been approved by the FDA for treatment of early-stage, HER2-positive breast cancer with remaining disease after surgery and initial post-surgery treatment. Patients who were treated with Kadcyla had 50% lower risk of developing invasive breast cancer or death than women in the Herceptin treatment group.

Share your thoughts on this XRAYS article by taking our brief survey.

Posted (6/17/19)

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Related Information and Resources

FORCE Information: Monoclonal antibodies (Herceptin)

FORCE XRAYS category: Cancer treatment

FORCE XRAYS category: Clinical trials

FORCE XRAYS category: Risk management

FORCE XRAYS category: Risk for recurrence

References

von Minckwitz G, Huang C-S, Mano MS, et al. “Trastuzumab Emtansine for Residual Invasive HER2-Positive Breast Cancer.” New England Journal of Medicine. Feb 14, 2019; 380(7): 617-628.

Statement of FDA approval of Kadcyla (ado-trastuzumab emtansine) for early breast cancer.

 

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