Practice-changing research in GI cancer

01/16/20 • 24 min

Daniel G. Haller, MD, of the University of Pennsylvania, Philadelphia, joins Blood & Cancer host David H. Henry, MD, also of the University of Pennsylvania, to review the top three GI cancer trials presented at the 2019 ESMO World Congress on Gastrointestinal Cancer, and how they are changing practice.

Plus, in Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University, talks about the difficulty in using age to guide cancer treatment.

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BEACON trial for colorectal cancer

Patients with BRAF mutations have a poor prognosis and typically fail treatment prior to second line therapy.
BEACON is a phase 3 trial that was designed to test BRAF/MEK combination targeted therapies in patients with BRAF-mutated metastatic colorectal cancer.
The study found that the three-drug combination of encorafenib, binimetinib, and cetuximab significantly improved overall survival in patients with BRAF-mutated metastatic colorectal cancer. The response rate for targeted triple therapy was 26%, compared with 2% for controls.
It may be important for all patients with colorectal cancer to be tested for BRAF.

IDEA trial in colon cancer

Use of oxaliplatin in chemotherapy treatment regimens results in improvement in outcomes for patents with stage III colon cancer. However, treatment with oxaliplatin can cause disabling neuropathy, which is directly proportional to the cumulative dose administered.
The IDEA (International Duration Evaluation of Adjuvant Therapy) trial combines data from six trials, in which patients with stage III colon cancer were randomized to receive 3 months or 6 months of adjuvant chemotherapy with a fluoropyrimidine plus oxaliplatin.
The incidence of peripheral neuropathy was significantly reduced with the 3-month regimen, as compared with 6- month treatment. Survival data for 3 months of treatment with oxaliplatin are still pending.
In patients with positive circulating tumor DNA (ctDNA) prior to adjuvant therapy, 6 months of treatment was preferable.

Pembrolizumab, plus or minus chemotherapy, in gastric cancer

This was a well-balanced three-arm study which included groups of patients treated upfront with pembrolizumab alone, chemotherapy alone, or a combination of pembrolizumab with chemotherapy. The primary endpoint was overall survival.
Pembrolizumab was noninferior to chemotherapy if the combined positive score (CPS) was greater than 1. Pembrolizumab plus chemotherapy was not superior, even for CPS greater than 0.85.
When pembrolizumab is started alone, patients drop off quickly. However, the responders to pembrolizumab have a long duration of response. It may be beneficial to start with chemotherapy and switch to targeted therapy when the side effects of chemotherapy become too great.

Show notes by Debika Biswal Shinohara, MD, PhD, resident in the department of internal medicine, University of Pennsylvania, Philadelphia.

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For more MDedge Podcasts, go to mdedge.com/podcasts

Email the show: [email protected]

Interact with us on Twitter: @MDedgehemonc

David Henry on Twitter: @davidhenrymd

Ilana Yurkiewicz on Twitter: @ilanayurkiewicz

Plus, in Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University, talks about the difficulty in using age to guide cancer treatment.

* *

BEACON trial for colorectal cancer

Patients with BRAF mutations have a poor prognosis and typically fail treatment prior to second line therapy.
BEACON is a phase 3 trial that was designed to test BRAF/MEK combination targeted therapies in patients with BRAF-mutated metastatic colorectal cancer.
The study found that the three-drug combination of encorafenib, binimetinib, and cetuximab significantly improved overall survival in patients with BRAF-mutated metastatic colorectal cancer. The response rate for targeted triple therapy was 26%, compared with 2% for controls.
It may be important for all patients with colorectal cancer to be tested for BRAF.

IDEA trial in colon cancer

Use of oxaliplatin in chemotherapy treatment regimens results in improvement in outcomes for patents with stage III colon cancer. However, treatment with oxaliplatin can cause disabling neuropathy, which is directly proportional to the cumulative dose administered.
The IDEA (International Duration Evaluation of Adjuvant Therapy) trial combines data from six trials, in which patients with stage III colon cancer were randomized to receive 3 months or 6 months of adjuvant chemotherapy with a fluoropyrimidine plus oxaliplatin.
The incidence of peripheral neuropathy was significantly reduced with the 3-month regimen, as compared with 6- month treatment. Survival data for 3 months of treatment with oxaliplatin are still pending.
In patients with positive circulating tumor DNA (ctDNA) prior to adjuvant therapy, 6 months of treatment was preferable.

Pembrolizumab, plus or minus chemotherapy, in gastric cancer

This was a well-balanced three-arm study which included groups of patients treated upfront with pembrolizumab alone, chemotherapy alone, or a combination of pembrolizumab with chemotherapy. The primary endpoint was overall survival.
Pembrolizumab was noninferior to chemotherapy if the combined positive score (CPS) was greater than 1. Pembrolizumab plus chemotherapy was not superior, even for CPS greater than 0.85.
When pembrolizumab is started alone, patients drop off quickly. However, the responders to pembrolizumab have a long duration of response. It may be beneficial to start with chemotherapy and switch to targeted therapy when the side effects of chemotherapy become too great.

Show notes by Debika Biswal Shinohara, MD, PhD, resident in the department of internal medicine, University of Pennsylvania, Philadelphia.

* *

For more MDedge Podcasts, go to mdedge.com/podcasts

Email the show: [email protected]

Interact with us on Twitter: @MDedgehemonc

David Henry on Twitter: @davidhenrymd

Ilana Yurkiewicz on Twitter: @ilanayurkiewicz

Previous Episode

Palliative care: Not just another word for hospice

Thomas LeBlanc, MD, of Duke Cancer Institute in Durham, N.C., joins host David H. Henry, MD, of Pennsylvania Hospital, Philadelphia, to discuss the evolution of the palliative care field and some of the underrecognized ways that it can improve care for hematology-oncology patients.

Plus, in Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University, shares the story of a patient who put aside her own desire for hospice because of family pressure to pursue curative treatment.

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Palliative medicine has evolved tremendously over the past decade; it used to be synonymous with hospice and dying. It is now a sophisticated medical subspecialty with growing and large evidence base.
Palliative treatments are aimed at maximizing patient's quality of life and can be provided alongside other curative treatments.
Physicians, physician assistants, and nurse practitioners form an interdisciplinary team along with patients and their families.
Palliative care specialists can work alongside oncologists to optimize symptom management in patients with multiple or refractory/severe symptoms, including chemotherapy-induced nausea and pain neuropathy.
Palliative care specialists also can help provide a safe space and an extra layer of support to patients having difficulty coping with illness.
The American Society of Clinical Oncology (ASCO) has developed a guideline that all patients with advanced cancer should be receiving dedicated palliative care services concurrent with active treatment.
Workforce shortages in palliative care are limiting access for patients with cancer.

Resource:

Integration of palliative care into standard oncology care: ASCO Practice Guideline update (2017)

Show notes by Debika Biswal Shinohara, MD, PhD, resident in the department of internal medicine, University of Pennsylvania, Philadelphia.

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For more MDedge Podcasts, go to mdedge.com/podcasts

Email the show: [email protected]

Interact with us on Twitter: @MDedgehemonc

David Henry on Twitter: @davidhenrymd

Ilana Yurkiewicz on Twitter: @ilanayurkiewicz

Next Episode

Sickle cell update: Treating pain and progress toward cure

When it comes to treating pain related to sickle cell disease, consider the underlying factors, from constipation to compression spine deformity. That’s just some of the advice from Ifeyinwa Osunkwo, MD, of Atrium Health and Levine Cancer Institute in Charlotte, N.C. She joins host David H. Henry, MD, of Pennsylvania Hospital, Philadelphia, to discuss her tips for treating pain and other complications of sickle cell disease. Dr. Osunkwo also provides an update on progress toward a cure in sickle cell disease that could be available to a large number of patients.

Plus, in Clinical Correlation, Ilana Yurkiewicz, MD, of Stanford (Calif.) University, talks about why treating patients with cancer doesn’t make her sad.

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Treating pain in sickle cell:

In sickle cell disease, patients have acute episodes of vaso-occlusive crisis, as well as chronic pain.
Consider whether the pain symptoms are an acute exacerbation of their chronic pain, an independent acute episode of pain, or chronic pain.
In her practice, Dr. Osunkwo has moved to less chronic opioid use and more adjuvant use. She says treat the pain but look for the reason underlying it. The pain could be a result of bone damage, a compression spine deformity, constipation, or other factors related to their disease or the treatment.
Consider the impact of opioid withdrawal after receiving a high dose in the hospital.

Treating acute chest syndrome:

Acute chest syndrome is usually not subtle in its presentation. It is acute and includes fever, pain, difficulty breathing or shortness of breath, hypoxia, and the patient looks sick.
Consider their last chest x-ray and look for changes. Is this a new pulmonary infiltrate?
This is a patient who should be transfused to get them out of distress.
Most of acute chest syndrome cases happen 3 days into a hospital admission.

Developments in sickle cell treatment:

Two new drugs to treat sickle cell symptoms were approved in the United States in 2019: voxelotor (Oxbryta) to increase hemoglobin and crizanlizumab-tmca (Adakveo) to reduce the frequency of vaso-occlusive crisis.
What is coming next? Researchers are working on potential cures for sickle cell that would be available to patients on a widespread basis. That includes haploidentical transplant and gene therapy.

American Society of Hematology guidelines on the treatment of sickle cell complications.

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For more MDedge Podcasts, go to mdedge.com/podcasts

Email the show: [email protected]

Interact with us on Twitter: @MDedgehemonc

David Henry on Twitter: @davidhenrymd

Ilana Yurkiewicz on Twitter: @ilanayurkiewicz