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AACR Study Presentations Include New Data in Breast and Prostate Cancers, Sarcoma, and High-Risk Individuals


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THE 2019 American Association for Cancer Research (AACR) Annual Meeting was held March 29 to April 3 in Atlanta. In addition to our regular coverage of news stories from the meeting, here are some brief highlights of additional noteworthy studies.

Stage IV HER2-Positive Breast Cancer: Surgery or No Surgery?

SURGERY FOR the primary tumor in patients diagnosed with metastatic HER2-positive breast cancer is controversial. In the post-trastuzumab era of effective targeted therapies for HER2-positive breast cancer, many patients with stage IV disease are treated with systemic therapy, and surgery is not offered. The effect of surgery on survival in this setting is not known.

A large retrospective review presented at the AACR meeting suggests that surgery to the primary tumor is associated with higher survival rates in stage IV HER2-positive breast cancer.1 The study was based on records from the National Cancer Database from 2010 to 2012. Case records of 3,231 women were identified; of these women, 89.4% were treated with chemotherapy or targeted therapy, 37.7% received endocrine therapy, and 31.8% had radiotherapy.


“These findings suggest that surgery to remove the primary tumor should be considered in addition to standard HER2-targeted medications and other adjuvant therapy if a woman has stage IV HER2-positive breast cancer.”
— Sharon Lum, MD

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A total of 1,130 women had surgery to the primary tumor. Surgery was associated with a 44% increased likelihood of survival.

“These findings suggest that surgery to remove the primary tumor should be considered in addition to standard HER2-targeted medications and other adjuvant therapy if a woman has stage IV HER2-positive breast cancer,” said senior author of this study, Sharon Lum, MD, Professor of Surgery, Loma Linda University Health, Loma Linda, California.

After controlling for covariates, the study authors found that women with Medicare were more likely to undergo surgery and less likely to die of breast cancer compared with those with Medicaid or no insurance. White women were more likely to have surgery and less likely to die of breast cancer than non-Hispanic black women.

“These results suggest that disparities in health care due to race and socioeconomic factors must be addressed,” said lead author Ross Mudgway, a medical student at the University of California, Riverside, School of Medicine.

Ross Mudgway

Ross Mudgway

The decision to have surgery rests on physician and patient factors, the authors noted. Age, comorbidity, and patient preference should be taken into account. They agreed that, based on a patient’s response to standard HER2-targeted therapy, surgery could be an option, but further study is needed. This retrospective study does not take into account whether patients were offered surgery and does not consider factors that influenced their decision. Final results from ongoing randomized clinical trials are needed to determine if there is a true survival benefit from surgery of the primary tumor in this setting.

HER2-Targeted CAR T Cells and Lymphodepletion in Sarcoma

IN A PHASE I clinical trial, combining chemotherapy with chimeric antigen receptor (CAR) T cells targeted to the HER2 protein was safe and engendered responses in children and adults with advanced HER2-positive sarcoma.2

“Children and adults with recurrent or refractory sarcoma have limited treatment options. Depending on the specific type of sarcoma, curative salvage regimens are available, but the chance of success is low and the therapies can be quite toxic,” said lead author Shoba Navai, MD, of Baylor College of Medicine, Houston.

HER2 is expressed in up to 40% of osteosarcomas, among the more common types of sarcoma. It is unknown what percentages of other types of sarcoma are HER2-positive. HER2 positivity is associated with more aggressive tumors, and previous studies have shown that HER2-directed therapies are effective in HER2-positive sarcomas.

“Experimental studies by our group have suggested that HER2-directed CAR T cells may have activity in patients with sarcoma even when HER2-antibody therapies do not,” she said. In the phase I trial, heavily pretreated patients with advanced sarcoma received up to three infusions of HER2-directed CAR T cells after lymphodepletion with fludarabine, with or without cyclophosphamide. Responders received up to an additional five infusions of CAR T cells without lymphodepletion.


“Experimental studies by our group have suggested that HER2-directed CAR T cells may have activity in patients with sarcoma even when HER2-antibody therapies do not.”
— Shoba Navai, MD

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The data Dr. Navai reported were based on 10 patients, aged 4 to 54 years, with refractory/metastatic HER2-positive sarcoma (5 with osteosarcoma, 3 with rhabdomyosarcoma, and 1 each with Ewing sarcoma and synovial sarcoma). CAR T-cell expansion was documented in all but two patients. The median peak expansion was on day 7, and CAR T cells were detectable in all patients 6 weeks after infusion.

The investigators observed two complete responses, four patients with stable disease, and four with progressive disease. Toxicities were limited, with no opportunistic infections, no pulmonary or cardiac toxicities, and no neurotoxicity. In one patient re-treated with CAR T cells who achieved a complete response, newly detected antibodies to CAR T cells after infusion suggested that the patient’s own immune system was engaged to fight the cancer, she said.

This is a small phase I trial with intriguing results in a disease with limited options. Thus, further study in larger groups of patients is warranted, Dr. Navai added.

Cardiovascular Risk and Abiraterone Acetate

PREEXISTING CARDIOVASCULAR disease was associated with an increased risk of mortality in men with advanced prostate cancer during the first 6 months of abiraterone acetate treatment, according to a retrospective study based on a large population-based data set.3 Six-month mortality rates ranged from 21.4% to 25.6% in patients with various types of preexisting cardiovascular disease vs 15.8% for those without preexisting cardiovascular disease.

“Our data show that patients who have preexisting cardiovascular disease experienced higher mortality after receiving abiraterone compared with those who do not, and the bulk of the survival differences occurred in the first 6 months of treatment,” noted lead author Grace Lu-Yao, PhD, MPH, Associate Director of Population Science at the Sidney Kimmel Cancer Center at Jefferson Health, Philadelphia. She noted that clinical trials of abiraterone acetate often exclude patients with cardiovascular disease, so results of these trials may not be generalizable to patients with cardiovascular morbidity.

“It is very important that patients with advanced prostate cancer understand that the outcomes of abiraterone acetate treatment reported in clinical trials may not apply to all patients treated in the real world, especially those who don’t meet the eligibility criteria of the clinical trials,” Dr. Lu-Yao said.


“Our data show that patients who have preexisting cardiovascular disease experienced higher mortality after receiving abiraterone acetate compared with those who do not, and the bulk of the survival differences occurred within the first 6 months of treatment.”
— Grace Lu-Yao, PhD, MPH

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The study was based on 2,845 patients in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database diagnosed with prostate cancer between 1991 and 2013 and treated with abiraterone acetate between 2011 and 2014. The median age was 75 years, and 1,924 patients (67.6%) had at least 1 preexisting cardiovascular condition.

The risk of dying within 6 months of the first dose was high for individuals with the following preexisting conditions: ischemic heart disease (21.4%), stroke (22.1%), congestive heart failure (23.4%), atrial fibrillation (24.4%), and acute myocardial infarction (25.6%). Moreover, the risk of hospitalization was increased in the 6 months after initiation of abiraterone acetate therapy compared with 6 months previously, regardless of the presence of preexisting cardiovascular disease. The rate of hospitalization increased by 53% in patients without cardiovascular disease and between 34% to 55% for those with cardiovascular disease.

The primary limitations include the retrospective nature of the study design, incomplete data on potential confounders, and lack of a control group.

HPV Vaccination Uptake Suboptimal for High-Risk Adults

PREVIOUS STUDIES have found that human papillomavirus (HPV) vaccination is underutilized in boys and girls during optimal ages for the prevention of HPV infection (11 through 15 years old). Underutilization of the HPV vaccine extends to adults as well. A new study has found that adults at high risk for human immunodeficiency virus (HIV) infection were less likely than the general population to be vaccinated against HPV, which is associated with anal and cervical cancers.4

Lisa T. Wigfall, PhD

Lisa T. Wigfall, PhD

In a healthy individual, HPV infection is often cleared from the body without causing disease. But HIV infection compromises the immune system, and an HIV-positive person may be more vulnerable to developing HPV-related cancer, explained lead author Lisa T. Wigfall, PhD, of Texas A&M University in College Station, Texas.

The study included 16,507 individuals who self-reported engaging in 1 or more high-risk behaviors for HIV in the previous year prior to completing the 2016 Behavioral Risk Factor Surveillance System survey. High-risk factors included intravenous drug use, a diagnosis of sexually transmitted disease, exchanging sex for money, unprotected anal sex, and four or more sex partners. Complete data on high-risk sexual behaviors were available for 416 individuals, Dr. Wigfall noted.

Rates of uptake of the vaccination were low: under 30% of heterosexual females, 20% of lesbian females, and 10% of heterosexual males initiated or completed the vaccine. Under 10% of gay males completed the vaccine, whereas 25% initiated it.

Although this study sends a cautionary message to doctors who treat individuals at high risk of HIV infection, the study had some limitations. For example, the researchers were not able to ascertain how many individuals who answered the survey were HIV-positive. Dr. Wigfall recommended improved patient-provider communication about the availability of the HPV vaccine and its benefits, especially among HIV-positive patients and patients who engage in high-risk behavior.

DISCLOSURE: Drs. Lum, Navai, Lu-Yao, and Wigfall and Mr. Mudgway reported no conflicts of interest.

REFERENCES

1. Mudgway R, de Paz Villanueva CC, Lin AC, et al: The impact of primary tumor surgery on survival in HER2 positive stage IV breast cancer patients in the current era of targeted therapy. 2019 AACR Annual Meeting. Abstract 4873. Presented April 3, 2019.

2. Navai SA, Derenzo C, Joseph S, et al: Administration of HER2-CAR T cells after lymphodepletion safely improves T cell expansion and induces clinical responses in patients with advanced sarcomas. 2019 AACR Annual Meeting. Abstract LB-147. Presented April 1, 2019.

3. Lu-Yao G, Keith SW, Gandhi K, et al: Clinical outcomes among patients treated with abiraterone acetate for advanced prostate cancer with pre-existing cardiovascular conditions. 2019 AACR Annual Meeting. Abstract 4469. Presented April 2, 2019.

4. Wigfall LT, Bynum AS, Wells J, et al: HPV vaccination among adults at high-risk for HIV infection: A public health priority. 2019 AACR Annual Meeting. Abstract 3327. Presented April 2, 2019.


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