ASCO Annual Meeting 2017: Advances in Immunotherapy for Multiple Myeloma and Mesothelioma, and Targeted Therapies for Non-Small Cell Lung Cancer and HER2-Positive Breast Cancer

2017 ASCO Annual Meeting. #ASCO17
June 5, 2017
Greg Guthrie, ASCO staff

“Although we span many disciplines and professions,” says ASCO President Daniel F. Hayes, MD, FACP, FASCO, “we are a single community with a singular focus: to provide better care for patients at risk for or with cancer.” That is why the theme of this year’s American Society of Clinical Oncology (ASCO) Annual Meeting is Making a Difference in Cancer Care WITH YOU. Watch a patient education video with Dr. Hayes explaining why the ASCO Annual Meeting is so significant.

More than 38,000 oncology professionals from around the world are at the ASCO Annual Meeting, presenting and discussing the latest research in treatment and patient care. Learn about the research released today:

  • CAR T-cell therapy sends multiple myeloma into remission

  • Early research suggests immunotherapy for mesothelioma may work

  • Alectinib halts ALK-positive lung cancer growth more than a year longer than crizotinib

  • Potential new targeted therapy for EGFR-positive lung cancer

  • Adding second HER2 blocker may help some women with breast cancer

CAR T-cell therapy sends multiple myeloma into remissionshare on twitter 

A phase I clinical trial conducted in China used a new type of immunotherapy to treat multiple myeloma, causing a remission in most patients within the small study. Immunotherapy is a treatment approach designed to boost the body’s natural defenses to fight the cancer.

The immunotherapy used in this study was a chimeric antigen receptor (CAR) T-cell therapy that targets B-cell maturation protein, also called BCMA. CAR T-cell therapy is custom-made for each patient. The patient’s own T cells are collected, genetically reprogrammed in a lab, and injected back into the patient. The reprogramming involves inserting an artificially designed gene into the T-cell genome, which helps the genetically reprogrammed cells find and destroy cancer cells throughout the body.

Multiple myeloma is a blood cancer in specific cells found in the bone marrow called plasma cells, which make antibodies to fight infections. Participants in this study were 35 people with multiple myeloma that had come back after treatment, called relapsed or recurrent, or was resistant to treatment, called refractory. Of those 35, 33 patients (94%) had a remission within 2 months of receiving the CAR T cells. So far, the researchers have been tracking the health of 19 of those patients for more than 4 months, and among them, 14 have experienced a complete remission, meaning the cancer cannot be detected in the body and there are no symptoms, and 5 had a partial remission. Only 1 patient had the cancer grow worse after treatment, and that patient first had a partial remission for 3 months. There are 5 patients who have been monitored by researchers for 12 to 14 months so far, and all have no detectable cancer cells in their bone marrow.

CAR T-cell therapy can have dangerous side effects, including cytokine release syndrome (CRS) and neurologic side effects. CRS occurred in 85% of the patients, but it was temporary and most patients had mild and manageable symptoms. CRS symptoms include fever, low blood pressure, difficulty breathing, and problems with different organs. Two patients had severe CRS but recovered. No patients had neurologic side effects.

The researchers plan to keep adding patients to this study until they reach 100 total patients. They also plan to launch a similar study in the United States in 2018.

What does this mean? This was a small, early study of CAR T-cell therapy to treat multiple myeloma, but the treatment’s effectiveness in the majority of the patients is encouraging.

“Although recent advances in chemotherapy have prolonged life expectancy in multiple myeloma, this cancer remains incurable. It appears that with this novel immunotherapy there may be a chance for cure in multiple myeloma, but we will need to follow patients much longer to confirm that.”

— study author Wanhong Zhao, MD, PhD
The Second Affiliated Hospital of Xi’an Jiaotong University
Xi’an, China

Early research suggests immunotherapy for mesothelioma may workshare on twitter 

Early findings from a phase II clinical trial in France indicate that immunotherapy may be an effective approach to treating people with malignant pleural mesothelioma (MPM) that has come back, or recurred, after standard chemotherapy. The research studied the use of 2 immunotherapy treatment plans, nivolumab (Opdivo) or a combination of nivolumab and ipilimumab (Yervoy), after a recurrence.

MPM is a rare cancer that begins in the lining surrounding the lungs. MPM is difficult to treat, and current treatment options have limited effectiveness. Chemotherapy is a standard treatment, but MPM is known to recur despite this treatment. Immunotherapy is a type of treatment designed to boost the body’s natural defenses to fight the cancer. The 2 drugs tested in this study are called immune checkpoint inhibitors.

Participants in this study had recurrent MPM and had received 1 or 2 previous treatments of chemotherapy. They were randomly assigned to 1 of 2 groups, either receiving nivolumab alone or the combination of nivolumab and ipilimumab. After 12 weeks of treatment, results on 108 participants were that the cancer had not worsened for 44% of patients who received nivolumab and 50% of patients who received both nivolumab and ipilimumab. For comparison, other treatments used for recurrent MPM stop the cancer from worsening in less than 30% of patients. Nivolumab shrank tumors in 17% of patients, and the combination shrank tumors in 26% of patients.

After a period of 10 months, the study included 125 participants. The study data showed that the median time it took for the cancer to worsen was 4 months for people treated with nivolumab and 5.6 months for those treated with nivolumab plus ipilimumab.

Common side effects were thyroid problems, colon inflammation, and skin rash. Severe side effects were more common in the nivolumab plus ipilimumab group.

What does this mean? This study indicates that immunotherapy may be a new treatment option for people with this hard-to-treat disease after a recurrence.

“Our findings suggest that immunotherapy may provide new hope to patients with relapsed mesothelioma. This randomized phase II trial may be enough to support the use of immune checkpoint inhibitors in this setting, but it is too early to conclude whether nivolumab alone or the combination of nivolumab and ipilimumab is better.”

— lead study author Arnaud Scherpereel, MD, PhD
University Hospital (CHU) of Lille
Lille, France

 

Alectinib halts ALK-positive lung cancer growth more than a year longer than crizotinibshare on twitter 

Alectinib (Alecensa) is a new targeted therapy that may be an effective first treatment for people with anaplastic lymphoma kinase (ALK)-positive non-small cell lung cancer (NSCLC). Results from a phase III clinical trial that tested alectinib against the current standard targeted treatment, crizotinib (Xalkori), found that alectinib lowered the risk of the cancer growing worse or of death by 53% compared with crizotinib. Alectinib also caused fewer severe side effects for patients.

ALK-positive NSCLC is diagnosed in about 12,500 people in the United States, or about 5% of all NSCLC diagnoses. ALK-positive means the cancer has a genetic change in the ALK gene. Crizotinib is an ALK inhibitor that has been the standard of care for several years. Although crizotinib initially works in most patients, the cancer typically starts growing again within a year. Alectinib is a more potent ALK inhibitor. It received U.S. Food and Drug Administration approval in 2015 for the treatment of people with advanced NSCLC that worsens despite taking crizotinib.

In this study, called ALEX, there were 303 patients with stage IIIB or stage IV ALK-positive NSCLC who took either alectinib or crizotinib as a first systemic treatment for their disease. It took about 15 months longer for the cancer to start growing again after treatment with alectinib when compared to crizotinib (25.7 months with alectinib vs. 10.4 months with crizotinib). After 1 year of treatment, brain metastases occurred less often in those who took alectinib (9%) than in those who took crizotinib (41%). Brain metastases means the spread of the lung cancer to the brain, and they have a significant impact on a person’s quality of life.

Side effects were less common with alectinib (41% of patients) than with crizotinib (50% of patients). The most common severe side effects of alectinib were fatigue, constipation, muscle aches, and swelling. Crizotinib most commonly caused gastrointestinal problems and liver enzyme abnormalities.

What does this mean? When compared to crizotinib, alectinib was more effective and caused fewer side effects. It may become a new standard of care in the treatment of ALK-positive NSCLC.

“Nobody imagined it would be possible to delay advanced lung cancer progression by this much. Most targeted therapies for lung cancer are associated with a median progression-free survival of roughly 12 months.”  

— lead study author Alice T. Shaw, MD, PhD
Massachusetts General Hospital Cancer Center
Boston, Massachusetts

Potential new targeted therapy for EGFR-positive lung cancershare on twitter

Findings from a phase III clinical trial indicate that a new targeted therapy, dacomitinib, is more effective than 1 of the standard targeted therapies used for non-small cell lung cancer (NSCLC) that has epidermal growth factor receptor (EGFR), called EGFR-positive cancer. However, the newer drug also caused more severe side effects.

EGFR-positive NSCLC is diagnosed in about 15,000 people in the United States alone and in about 140,000 people worldwide. EGFR-positive cancers have genetic changes that lead to an overactive EGFR protein, which fuels the growth of cancer cells. EGFR tyrosine kinase inhibitors (TKIs) have been the standard treatment for people with newly diagnosed EGFR-positive NSCLC for several years. This study compared a “first generation” EGFR inhibitor called gefitinib (Iressa) with a more powerful “second generation” EGFR inhibitor, dacomitinib. Dacomitinib is currently only available through research studies. The only second-generation EGFR TKI approved to treat NSCLC by the U.S. Food and Drug Administration (FDA) is afatinib (Gilotrif).

This study included 452 patients from Asia and Europe with newly diagnosed stage IIIB or stage IV EGFR-positive NSCLC. Participants were put into 2 groups, with 1 group receiving gefitinib and the other group receiving dacomitinib. Patients who received dacomitinib had a 41% lower chance of the cancer getting worse or of dying than those who received gefitinib. Patients who took dacomitinib lived nearly 15 months without the cancer progressing, compared to just over 9 months for those who took gefitinib. Researchers need more time to track the patients to better determine the differences between the drugs.

Common severe side effects from dacomitinib included acne and diarrhea, and 3 out of every 5 patients in this study had to lower their dose of dacomitinib because of side effects. The most common severe side effect of gefitinib was liver enzyme abnormalities.

What does this mean? Dacomitinib looks to be an effective new option in the treatment of EGFR-positive NSCLC, but patients and doctors should carefully consider the risk of severe side effects.

“We changed the treatment paradigm for EGFR-positive lung cancer a few years ago when targeted therapy replaced chemotherapy. This study shows that dacomitinib may be an even more effective treatment for these patients. However, patients should be aware of the need to deal with potential side effects when making treatment decisions.”

— lead study author Tony Mok, MD
Chinese University of Hong Kong
Hong Kong, China

Adding second HER2 blocker may help some women with breast cancershare on twitter 

Results from a phase III clinical trial with women with HER2-positive breast cancer suggest that adding a second HER2 targeted therapy, pertuzumab (Perjeta), to the standard treatment of trastuzumab (Herceptin) after surgery may help, although the benefits appear modest.

In this study, 4,805 women with HER2-positive, early-stage breast cancer were randomly assigned to 1 of 2 groups after they had surgery to remove the cancer and chemotherapy for 18 weeks. The first group then added 1 year of trastuzumab alone and the second group took both trastuzumab and pertuzumab for 1 year.

Invasive breast cancer begins in the milk ducts or glands and spreads into surrounding tissue. From there, it can spread to nearby lymph nodes and beyond. Treatment with trastuzumab has previously proven to be very effective in reducing a woman’s risk of risk of cancer returning. However, patients who received pertuzumab and trastuzumab had a 19% lower chance of developing invasive breast cancer than those who received only trastuzumab.

At 3-year follow-up, 93.2% of women who received trastuzumab alone had not developed invasive disease compared with 94.1% of those who received pertuzumab and trastuzumab, a small difference of 1%. Among women who had cancer that had spread to the lymph nodes (63% of the patients in this study), the pertuzumab was slightly more effective at stopping the invasive disease than trastuzumab alone (92% vs. 90.2%). At a median follow-up of almost 4 years, 171 (7.1%) patients in the pertuzumab group had developed invasive breast cancer, compared to 210 (8.7%) patients in the trastuzumab-only group.

The rates of serious side effects were low and similar in both groups, except for diarrhea. Heart failure or heart-related death occurred in 0.7% of patients in the group that took both drugs and in 0.3% of patients in the trastuzumab-only group. Severe diarrhea was more common with the pertuzumab group, occurring in 9.8% of patients, compared to 3.7% of those who received only trastuzumab.

What does this mean? Adding pertuzumab to standard treatment might help some women with HER2-positive breast cancer, but patients should talk with their doctor about this based on their personal risk level of the disease returning after treatment

“Our early findings suggest that we may be able to further improve outcomes for some women by adding a second HER2-targeted treatment, without increasing risk for serious side effects…These are very early results, but given that the absolute benefit from adding pertuzumab was modest, we should consider using it primarily in women with the highest risk—those with node-positive and hormone receptor-negative breast cancer.

— lead study author Gunter von Minckwitz, MD, PhD
German Breast Group
Neu-Isenburg, Germany

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