Thank you New Orleans! Thoughts from 2012 Congress


Thank you New Orleans for your Southern hospitality and charm..and food! Our SIG was involved in many events at the 2012 Congress. We displayed our SIG poster in the main hall, sponsored many well-received sessions, and had a very vibrant and engaged networking meeting.

Our new Coordinator-Elect, Carolyn Hendrix, was introduced at the SIG meeting and I would like to offer a very warm welcome and congratulations to her. I know that Carolyn, myself, and Brenda Keith (coordinator-ex-officio) are committed to continue building our SIG to meet our goals of providing pertinent clinical information to nurses caring for patients treated with targeted therapies. We want to hear your concerns, your needs, and your ideas! Please never hesitate to contact any of of us: Coordinator: Kristine Abueg at mailto:kdeano@hotmail.comor kristine.d.abueg@kp.org Coordinator-Elect: Carolyn Hendrix, RN, MSN, OCN® at carolyn.hendrix@hoag.org Coordinator Ex-Officio: Brenda K. Keith, RN, MN, AOCNS® at bkeith@gene.com

Having just gotten off the plane…I going to take this week to compile the notes we’ve gathered at Congress and start posting and responding to comments.

With thanks, Kristine

What's New in HER2


As promised during the session, I'm posting the full slide set from the presentation "What's new in HER2: Updates in HER2 positive Breast Cancer Treatment."  Look for the link on the folder section on the Resources page. 

HER

Investigational Targeted Drug Induces Responses in Aggressive Lymphomas

http://www.nih.gov/news/health/apr2012/nci-02.htm

Investigational targeted drug induces responses in aggressive lymphomas

Preliminary results from clinical trials in a subtype of lymphoma show that for a number of patients whose disease was not cured by other treatments, the drug ibrutinib can provide significant anti-cancer responses with modest side effects.These results were presented as part of the opening plenary session at the American Association of Cancer Research (AACR) Annual Meeting 2012 on April 1 by researchers at the National Cancer Institute (NCI), part of the National Institutes of Health, and colleagues.

Lymphomas are the fifth most common form of cancer. They are caused by an abnormal proliferation of white blood cells, can occur at any age, and are often marked by lymph nodes that are larger than normal, fever, and weight loss. Diffuse large B-cell lymphomas (DLBCL), which were studied in this trial, are aggressive cancers that grow rapidly and represent 30 percent to 40 percent of newly diagnosed lymphomas. DLBCL originates from B cells, which play a crucial role in the body's immune response.

There have been no major advances in the treatment of DLBCL in more than a decade. However, important advances have been made in understanding that this disease is comprised of at least three molecular subtypes, each derived from B cells at unique stages in their development. The activated B-cell (ABC) subtype of DLBCL accounts for approximately 40 percent of cases and has the poorest clinical outcome with current therapy.

Recent genetic studies have revealed that chronic activity of receptors that sit on the surface of B cells play an important role in the progression of ABC lymphomas. In normal B cells, these B-cell receptors help the cells recognize infections. In malignant B cells of ABC lymphomas, these receptors provide crucial signals that promote tumor cell survival. Over one-fifth of ABC tumors have mutations that alter the activity of the B-cell receptor. Based on these findings, researchers looked for ways to target B-cell receptor signaling therapeutically. This research identified the enzyme Bruton's tyrosine kinase (BTK) as a key element in the B-cell receptor pathway that is required to maintain the survival of ABC lymphoma cells.

"Our trial is a prime example of precision medicine," said Louis Staudt, M.D., Ph.D., deputy chief, Metabolism Branch at NCI. "A better understanding of the changes in cancer cells is leading us to what we hope will be more effective treatment strategies tailored to the genetic profile of each patient’s cancer."

Based on this molecular research, investigators chose to use the drug ibrutinib (formerly PCI-32765), a potent inhibitor of BTK, in their clinical trials. Ibrutinib is an oral, highly specific and irreversible inhibitor of the BTK enzyme. Pharmacyclics Inc., Sunnyvale, Calif., and Janssen Research and Development, L.L.C., Horsham, Pa., are developing the drug to target B-cell malignancies, including various forms of leukemia, lymphoma and multiple myeloma.

In studies led by Staudt and his NCI colleague, Wyndham Wilson, M.D., ibrutinib was first evaluated in a pilot trial at NCI in ABC DLBCL, and is now being evaluated in an ongoing multicenter study in DLBCL. Results from the pilot trial and individual cases from the ongoing trial indicate that the use of the single agent pill form of ibrutinib can elicit major anti-lymphoma effects with minimal side effects.

Participants in these studies were given ibrutinib as a pill at a fixed dose of 560 milligrams daily until the disease progresses. Ibrutinib induced multiple responses including some complete remissions in ABC lymphomas. Remissions were also observed in patients with non-ABC DLBCL, suggesting a broader role for the B-cell receptor pathway in this type of lymphoma. A final analysis will provide additional insights into the safety and efficacy of ibrutinib in the treatment of DLBCL.

"These results illustrate how an understanding of the molecular machinery inside a cancer cell can lead to new therapies which can kill tumor cells while sparing normal cells, thus greatly reducing toxicities for patients," said Staudt.

To read details about this trial (identifier # NCT01325701), please go to

http://clinicaltrials.gov/ct2/show/NCT01325701?term=PCI-32765&cond=lymphoma&rank=5.

NCI leads the National Cancer Program and the NIH effort to dramatically reduce the burden of cancer and improve the lives of cancer patients and their families, through research into prevention and cancer biology, the development of new interventions, and the training and mentoring of new researchers. For more information about cancer, please visit the NCI Web site at

www.cancer.gov or call NCI's Cancer Information Service at 1-800-4-CANCER (1-800-422-6237).

About the National Institutes of Health (NIH):

NIH, the nation's medical research agency, includes 27 Institutes and Centers and is a component of the U.S. Department of Health and Human Services. NIH is the primary federal agency conducting and supporting basic, clinical, and translational medical research, and is investigating the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit www.nih.gov.

NIH...Turning Discovery Into Health

Targeted Therapy News - Bevacizumab 1/12/2012

By now you may have heard in the news about changes in bevacizumab indication by the FDA. Bevacizumab will still remain on the market as an approved treatment for certain types of colon, lung, kidney and brain cancer (glioblastoma multiforme); however, as described below breast cancer will be removed as an indication. The text below is from the NCI website (http://www.cancer.gov/cancertopics/druginfo/fda-bevacizumab) accessed 01/12/2012:

On November 18, 2011, Food and Drug Administration Commissioner Margaret Hamburg revoked the agency’s accelerated approval of the breast cancer indication for bevacizumab (Avastin®, made by Genentech). Bevacizumab used for metastatic breast cancer has not been shown to provide a benefit, in terms of delay in the growth of tumors, that would justify its serious and potentially life-threatening risks. Nor is there evidence that use of bevacizumab will either help women with breast cancer live longer or improve their quality of life.

This decision involves bevacizumab used in combination with the cancer drug paclitaxel for those patients who have not been treated with chemotherapy for their form of metastatic breast cancer known as HER2 negative. This indication must now be removed from bevacizumab's product labeling.

Bevacizumab was approved for metastatic breast cancer in February 2008 under the FDA’s accelerated approval program, which allows a drug to be approved based on data that are not sufficiently complete to permit full approval. The accelerated approval program provides earlier patient access to promising new drugs to treat serious or life-threatening conditions while confirmatory clinical trials are conducted. If the clinical trials do not justify the continued approval of the drug or a specific drug indication, the agency may revoke its approval. In this case, the accelerated approval was based on promising results from one study that suggested that the drug could provide a meaningful increase in the amount of time from when treatment is started until the tumor grows or the death of the patient.

After the accelerated approval of bevacizumab for breast cancer, the drug’s sponsor, Genentech, completed two additional clinical trials and submitted the data from those studies to the FDA. These data showed only a small effect on tumor growth without evidence that patients lived any longer or had a better quality of life compared to taking standard chemotherapy alone – not enough to outweigh the risk of taking the drug.

FDA's Center for Drug Evaluation and Research, which is responsible for the approval of this drug, ultimately concluded that the results of these additional studies did not justify continued approval and notified Genentech it was proposing to withdraw approval of the indication. Genentech did not agree with the Center’s evaluation of the data and, following the procedures set out in FDA regulations, requested a hearing on the Center’s withdrawal proposal, with a decision to be made by the Commissioner. That hearing took place June 28-29, 2011.

Dr. Hamburg has now made her decision based on a review of the arguments and evidence presented at the hearing, briefs filed by both CDER and Genentech before and after the hearing, public comments and data from multiple clinical trials.

Vismodegib  (Erivedge ®, Seattle Genetics)

Target

Hedgehog Pathway

Mechanism of Action

Inhibition of the Smoothened (SMO) protein of the Hedgehog pathway (Hh).  Crucial in embryogenesis, the Hh pathway is less active in maturity.  In cancer cells, Hh pathway appears to be more active.  Inhibition of the SMO component prevents activation of the Hh pathway.

Indications

  • Adult metastatic basal cell carcinoma, or locally advanced basal cell carcinoma that has recurred following surgery, or is unresectable.

Drug Administration:

Oral 150 mg daily with or without food until progression or unacceptable toxicity.  Available in 150 mg capsules.

 

Key Side Effects (>10%)

 

  • Muscle spasm
  • Alopecia
  • Dysgeusia
  • Weight loss
  • Arthalgias
  • vomiting
  • Fatigue
  • Nausea
  • Diarrhea
  • Decreased appetite
  • Constipation
  • ageusia
 

Key Patient Education

  • Swallow whole, do no crush.  If a dose is forgotten do not “double up next dose” or “make up”  as skipped dose.  Take next dose as scheduled.
  • The capsule has a pink opaque body and a grey opaque  cap, with “150 mg” printed on the capsule body and “VISMO” printed on the capsule cap in black.
  • Documented drug interactions with P-glycoprotein inhibitors (erithryomycin, azithromycin, etc) and drugs that alter gastric pH.  Patients should consult with their oncologists before taking any other medications.
  • Drug is potentially embryo toxic – patients should be counseled about risks related to pregnancy.

References

  • Wilkes, G (2012) Vismodegib, a Hedgehog Pathway Inhibitor for Adults with Locally Advanced or Metastatic Basal Cell Carcinoma,  Oncology: Nurse Edition, 26(8).
  • ERIVEDGE  (vismodegib) capsule for oral use, FDA package insert 01/2012



Brentuximab (Adcetris®, Seattle Genetics)

Target

CD-30 cell membrane protein

Mechanism of Action

Conjugated Monoclonal Antibody: anti-CD30 molecule linked to the cytotoxic agent MMAE (monomethyl auristatin E)

 

Dual mechanism of action:

1)    ADCC: Antibody dependent cellular toxicity driven by the action of the monoclonal antibody specific for CD30

2)    Internalization of the MMAE chemo leading to apoptotic cell death.

Indications

  • Hodgkin lymphoma (HL) after failure of autologous stem cell transplant (ASCT)
  • HL in patients who are not ASCT candidates after failure of at least 2 multiagent chemotherapy regimens1
  • Systemic anaplastic large cell lymphoma (sALCL) after failure of at least 1 multiagent chemotherapy regimen1

 

Drug Administration:

Intravenous

1.8mg/kg over 30 minutes every 3 weeks. 

The dose for patients weighing greater than 100 kg should be calculated based on a weight of 100 kg

Continue treatment until a maximum of 16 cycles, disease progression, or unacceptable toxicity.

 

Infusion Reactions

  • Have been observed in clinical trial (infrequent).  Patients should be observed for signs of infusion-related reactions.
  • Patients who have experienced a prior infusion-related reaction should be premedicated for subsequent infusions

Key Side Effects (>10%)

 

  • 54% of patients experienced peripheral neuropathy (PN) in clinical trials – most cases were Grade 1 or 2.  Patients should be monitored for symptoms of PN with new or worsening signs reported to the treating practioner.
  • Other commonly reported side effects (grade 1 or 2): fatigue, nausea, diarrhea.
  • Grade 3 neutropenia was reported in 20% of patients.  Doses should be held for severe neutropenia until resolution or return to baseline. Growth factor support should be considered for subsequent cycles.

References

  • Younes, et al (2010) Brentuximab Vendotin (SGN035) for relapsed CD-30 positive lymphomas. NEJM, 363:1812-21
  • ADCETRIS [Prescribing Information]. Bothell, WA: Seattle Genetics Inc; 2012


Pertuzumab (Perjeta ®, Genentech)

Target

HER2.  Binds to a unique site on the HER2 molecule  subdomain II (distinct from the trastuzumab binding site).

Mechanism of Action

Unconjugated monoclonal antibody specific for the  subdomain II of the HER2 molecule

 

Prevents HER2 dimerization with other HER2 receptors (especially HER3), inhibiting cell signaling pathways.

Indications

Metastatic HER2+ breast cancer, first line.  Given in combination with trastuzumab and Docetaxel.

Drug Administration:

IV.  Loading dose of 840 mg over 60 minutes.  Maintenacne doses of 420 mg q3 weeks over 30 to 60 minutes.

Infusion Reactions

  • Observed in clinical trial: pyrexia, chills, fatigue, headache, asthenia, hypersensitivity, and vomiting.
  • Observe patients closely for the first 60 minutes after the first infusion, and 30 minutes after subsequent infusions.
  • In clinical trials, on the first day, when only pertuzumab was administered, the overall frequency of infusion reactions was 13.0% in the pertuzumab-treated group and 9.8% in the placebo-treated group. Less than 1% were grade 3 or 4.

Key Side Effects (>30%)

In combination with trastuzumab and docetaxel

  • diarrhea, alopecia, neutropenia, nausea, fatigue, rash, and peripheral neuropathy.

Key Patient Education

  • LVEF dysfunction has been observed with Pertuzumab, at a rate comparable to trastuzumab.  Patients should be routinely monitored for LVEF decreases (every 3 months) to ensure that LVEF remains above the institution nomal limits, or does not demonstrate a significant decrease from baseline.
  • Women of child bearing potential should not get pregnant since Pertuzumab carries risk of embryo-fetal death and birth defects.  

References

Baselga, et al (2012) Pertuzumab plus Trastuzumab plus Docetaxel for Metastatic Breast Cancer, NEJM, 366, 109-119.

PERJETA (Pertuzumab) prescribing information, FDA package insert, 2012.

 



2014 Chemotherapy/Biotherapy Course Changes


Learn more about the changes to the 2014 Chemotherapy/Biotherapy Course with these Frequently Asked Questions.