Ariana Pelosci

Prevailing treatment strategies for oligometastatic breast cancer involve stereotactic body radiotherapy or surgical resection plus standard of care (SOC) systemic therapy based on prior data suggesting progression-free survival (PFS) and overall survival (OS) benefit, but truly randomized studies examining these methods are lacking.

Steven J. Chmura, MD, PhD, professor of radiation and cellular oncology, director of Clinical and Translational Research for Radiation Oncology, and Scientific Director of Cancer Clinical Trials at the University of Chicago Medicine, recently presented data from the phase 2R/3 NRG-BR002 trial (NCT02364557) that tested metastases-directed therapy (MDT) plus systemic therapy vs systemic therapy alone in patients with newly diagnosed oligometastatic breast cancer at the 

2022 American Society of Clinical Oncology (ASCO) Annual Meeting

. Results of the trial showed no benefit to the addition of MDT, with a median PFS of 23 months (70% CI, 18-29) vs 19.5 months (70% CI, 17-36), respectively (HR, 0.92; 70% CI, 0.71-1.17; 1-sided log-rank 

In an interview with CancerNetwork®, Chmura spoke about how results of the trial should influence his colleagues to consider different treatment options before subjecting their patients to potentially inefficacious treatment.

Q: What was the rationale for this research?

A: The overarching idea here is that we should view metastatic disease as a continuum, as something that can present on the one end as being quite widespread but on the other end as something with few areas and probably slow progression. If that continuum exists, then could we be intervening early in that cascade? Could we stop things in their tracks? The idea then is that if you intervene, [you may be able to] improve things like PFS and OS.

Q: What were the key findings of this research that stood out?

A: Prior to this study, there were innumerable single-institution, single-arm studies that showed great promise. Women who had limited spread of oligometastases, if they were treated aggressively, lived a long time and did quite well. [Different treatments were] never randomized in a true fashion to control for that. The outcome [of this study] shows why we have to [rely on] science. Talking about real-world data is fine, but it doesn’t tell us anything because those same real-world data had [everyone] assuming this worked. The bottom line is that it doesn’t work. It’s true that patients who present with a limited spread of disease do very well; systemic therapies work extremely well, and survival is fantastic. But it has nothing to do with the actual local intervention.

Q: How can these data be geared towards multidisciplinary practices?

A: If you do surveys and you look at the practice pattern—insurance even pays for these high-tech procedures to be done in first-line [setting]—in metastatic breast cancer, it has big implications. It should be stopped outside of clinical trials because any extra intervention you [perform] adds not only cost but a true potential for harm. I would hope this sort of routine practice, which has become quite common, comes to an end.

Q: How will this research potentially impact the treatment paradigm for this patient population?

A: Around 70% to 80% of patients are offered [systemic therapy plus local intervention] and they shouldn’t be. It should stop. The question is going to be whether there are competing forces to keep it going. It’ll be a question of how quickly it does stop and when. I don’t think that’s to say there may be populations this could help. Doing more studies is needed. If a woman has a very limited spread and they’re HER2 positive, if you just view them as one big group, adding this very expensive and potentially toxic therapy on top isn’t going to do any good.

Q: What do you hope your colleagues took away from this presentation?

A: The study was incredibly well done. The patients, staff, and everybody involved really put their bias aside and got it done. I think it became hard to even accrue patients because everybody assumed [the prevailing standard treatment strategy] would work. Anytime you randomized somebody to [a study arm in which they are not receiving] treatment, it’s hard to sell that. I hope they take away the quality of it and how definitively negative the results were. There’s no room for thinking maybe it works here or there. It just does not work.

Chmura SJ, Winter KA, Woodward WA, et al. NRG-BR002: A phase IIR/III trial of standard of care systemic therapy with or without stereotactic body radiotherapy (SBRT) and/or surgical resection (SR) for newly oligometastatic breast cancer (NCT02364557). 

. 2022; 40(suppl 16):1007. doi: 10.1200/JCO.2022.40.16_suppl.1007

This article originally appeared on Cancer Network®.

Articles

Steven J. Chmura, MD, PhD, discussed recent findings from the phase 2R/3 NRG-BR002 trial in patients with newly diagnosed oligometastatic breast cancer.

Steven J. Chmura, MD, PhD, compares addition of metastases-directed therapy vs SOC alone for oligometastatic breast cancer

Those who live in rural areas were reported to have higher levels of cancer fatalism and an overload of cancer information compared with individuals living in urban areas, according to a new study published in 

Cancer Epidemiology, Biomarkers, and Prevention

Rural residents were more inclined to believe that everything causes cancer (OR, 1.29; 95% CI, 1.17-1.43), prevention is not possible (OR, 1.34; 95% CI, 1.19-1.51), there are too many recommendations to prevent cancer (OR = 1.26; 95% CI, 1.13-1.41), and cancer is always fatal (OR = 1.21; 95% CI, 1.11-1.33) when compared with their urban counterparts. These concepts were referred to as the study’s “4 core beliefs.”

“Addressing this disparity is difficult on multiple levels, but perhaps most challenging is that rural adults often bypass cancer prevention and detection resources when they are made available. Trying to understand the reasons behind this behavior is a pressing task for cancer researchers. Our research hypothesis was that beliefs and attitudes about cancer may be the underlying cause, and that rural adults might be more prone to negative beliefs about cancer, possibly as a way to cope with limited access and resources,” lead investigator Jakob Jensen, PhD, a professor in the Department of Communication at the University of Utah, said in a press release.2

Investigators collected data from 12 centers, which included 3821 patients from rural areas and 6541 from urban areas. The majority of participants were non-Hispanic White (82.7%), although centers in the South, especially in rural areas, had a higher number of non-Hispanic Black individuals vs other centers (39.4% vs 22.0%). This was the case for the University of Alabama and Virginia Commonwealth University.

It was noted that while it wasn’t pertinent to the study to evaluate actual screening practices, it was important to discuss gender and eligibility for cancer screenings. Among women who were between the ages of 21 to 65 years, 21.9% were evaluable for cervical cancer screening. Additionally, 24.5% of women over 50 years of age were eligible for a mammography and 49.3% of individuals over the age of 50 years were eligible for a colorectal screening. At initial screening, 9.6% of participants indicated that they were current smokers, but not enough data was collected to determine if they were eligible for low-dose CT lung cancer screening.

When comparing between rural and urban residents, investigators noted significant differences. Those in rural areas were older, White, and were more likely to be female, have lower income, abd be less educated. Additionally, the population was more likely to be retired, be receiving Medicare, married, a smoker, and classified as obese according to their body mass index.

When looking at the 4 core beliefs the study was investigating, rural residents were more likely to respond that they agree or strongly agree with all 4 beliefs (

As investigators accounted for other demographic or lifestyle variables, the associations remained. The multivariate analysis found that individuals who had lower educational attainments and were smokers were more likely to agree with the four cancer beliefs statements. Additional variables that remained significant were age, sex, race or ethnicity, income, trouble paying medical bills, employment, and marital status. However, these were not significant in the 4 cancer belief outcome measures.

“Our findings are in line with previous research showing that this type of thinking might be a consequence of a wider cultural setup that fosters self-reliance and coping beliefs in response to stress and lack of resources. This is known as the psychological stress and coping theory. The findings of our study are consistent with this logic as populations with fewer resources (in this case, rural adults) are more likely to reduce (fatalism) or revise (overload) the situation,” Jensen concluded.

This article was originally published on Cancer Network.

1. Jensen JD, Shannon J, Iachan R, et al. Examining rural-urban differences in fatalism and information overload: data from 12 NCI-designated cancer centers. 

. 2022;31(2):393-403. doi:10.1158/1055-9965.EPI-21-0355

2. Rural residents tend to hold fatalistic beliefs and perceive more cancer-related information overload than urban residents. News Release. American Association for Cancer Research. January 28, 2022. Accessed on February 1, 2022. https://bit.ly/35H3SS8

Cancer misinformation may be more prevalent among residents in rural vs urban areas, study finds.

Cancer fatalism common among rural residents

The FDA has granted priority review for olaparib (Lynparza) for patients with 

-mutated HER2-negative high-risk early breast cancer who have previously been treated with chemotherapy before or after surgery, according to a press release from the PARP inhibitor’s developer, AstraZeneca.1

Olaparib was assessed as part of the phase 3 OlympiA trial (NCT02032823). which showed that patients had an improvement in invasive disease-free survival (iDFS), reducing the risk of breast cancer recurrence by 42% compared with those in the placebo group (HR, 0.58; 99.5% CI, 0.41-0.82; 

 <.0001). A prescription drug user fee act date has been set for early 2022.

A total of 1836 patients, including 6 men, were randomly assigned to receive either olaparib at 300 mg or the matching placebo twice daily for 52 weeks.2 In the intent-to-treat population, the median follow-up was 2.5 years. Additionally, 82.2% of patients had triple-negative breast cancer. Half of all patients received adjuvant chemotherapy and half received neoadjuvant chemotherapy. In 72.3% of patients, 

At the prespecified interim analysis, the efficacy boundary was crossed. At 3 years, a total of 85.9% of patients in the olaparib group and 77.1% of patients in the placebo group were alive and free of invasive disease. A total of 106 patients in the olaparib group and 178 in the placebo group experienced invasive disease or death.

At 3 years, the distant DFS was 87.5% in the olaparib group and 80.4% in the placebo group. Those who received olaparib had significantly longer distant DFS compared with the placebo group (HR, 0.57; 99.5% CI, 0.39-0.83; 

 <.001). In the olaparib group, 59 deaths were reported compared with 86 in the placebo group (HR, 0.68; 99% CI, 0.44-1.05; 

 = .02). In 93% patients in the olaparib group and 95% in the placebo group, the primary cause of death was breast cancer. Two patients who did not have a previous event of invasive disease died in the olaparib group. 

The safety analysis included 911 patients from the olaparib group and 904 in the placebo group. Discontinuation of treatment occurred in 25.9% patients in the olaparib group and 20.7% in the placebo group.

Adverse effects (AEs) of grade 3 or higher in the olaparib group included anemia (8.7%), decreased neutrophil count (4.8%), decreased white-cell count (3.0%), fatigue (1.8%), and lymphopenia (1.2%). Within the placebo group, AEs of grade 3 or higher did not occur in more than 1% of patients. A total of 5.8% patients in the olaparib group and 0.9% in the placebo group received blood transfusions, with 4.1% patients in the olaparib group only receiving 1 transfusion.

Serious AEs were repoted in 8.7% of patients in the olaparib group and 8.4% in the placebo group. In the olaparib group, 1 patient had cardiac arrest that led to death, and 1 patient in the placebo group developed acute myeloid leukemia (AML) and ovarian cancer. AEs of special interest included pneumonitis, radiation pneumonitis, myelodysplastic syndrome, or AML.

In the United States, Olaparib has been previously approved for first-line maintenance treatment of 

-mutated ovarian cancer following response to platinum-based chemotherapy, first-line maintenance treatment plus bevacizumab (Avastin) for homologous recombination deficient–positive advance ovarian cancer, and 

-mutated HER2-negative metastatic breast cancer previously treated with chemotherapy, with additional indications for treatment in prostate and pancreatic cancer.

This article was originally posted on Cancer Network®. 

1. Lynparza granted priority review in the US for BRCA-mutated HER2-negative high-risk early breast cancer. News Release. AstraZeneca. November 30, 2021. Accessed November 30, 2021. https://bit.ly/3llGA9m

2. Tutt ANJ, Garber JE, Kaufman B, et al. Adjuvant olaparib for patients with BRCA1- or BRCA2-mutated breast cancer. 

. 2021;384(25):2394-2405. doi:10.1056/NEJMoa2105215

Olaparib, which was granted priority review by the FDA, has been shown to improve invasive disease-free survival for patients with BRCA-mutated HER2-negative high-risk early breast cancer.

 FDA grants olaparib priority review in BRCA-mutated HER2-negative high-risk early breast cancer

Consideration for the whole family and psychosocial supports needs is particularly important for patients with breast cancer who have dependent children, with those who have a poor health-related quality of life (HRQOL), little social support, and single mothers having higher psychosocial needs, according to a study published in 

Findings from the study indicated that that 59.3% of patients with children expressed a current phycological support need and 33.3% expressed needs for their children. A bivariate association was identified indicating that a lack of social support and a poor maternal HRQOL resulted in higher psychosocial need among patients and their children.

A total of 561 patients met the study’s inclusion criteria and filled out a questionnaire, 23.0% of whom had received psychosocial support with their family prior to the rehabilitation program. For patients living in a metropolitan area, 30.4% had previously utilized psychosocial support compared with 17.4% of patients in rural areas. Psychosocial services were more frequently used by those who did not have a partner (34.5%), compared with patients who had a partner (20.5%). Additionally, 74.7% of patients who had not previously received family-centered psychosocial support felt that they had sufficient support from home, 48.5% did not feel a need for the services, and 42.3% did not know about the support offers.

In total, 87.1% expressed a need to support their children processing the disease, with 84.6% desiring support to determine whether their child’s reaction was appropriate. Moreover, 73.3% wanted support for their partners. Statements that referred to the patients' behavior, such as discussing their disease within the family, were less approved compared with statements regarding the well-being of the family as a whole.

Patients stated that family-centered support was mostly needed during the diagnostic stage (62.0%) and treatment stage (73.4%). In total, 24.4% of patients felt a need for family-centered support when finishing treatment, in addition to 22.3% who required support during rehabilitation. Additionally, 6.3% of patients did not specify the need for support. Over time, the need for psychosocial support remained stable (36.8%), and 33.1% did not need psychosocial support. Additionally, 17.9% had an increased need for support and 12.2% had a decreased need.

When seeking support, 81.4% of patients saw a psycho-oncologist and 12.7% used a professional counseling center.

If the patient did not have a partner, children trended towards having higher psychosocial support needs (51.3%) compared with patients who had a partner (29.6%). Additionally, patients less often expressed a need for psychosocial services for their partner and whole family (25.8% vs 22.9%).

Those without immediate social support or network tended to have higher psychosocial needs for themselves (76.1% vs 57.9%) and their children (63.2% vs 31.4%).

Patients who were reported to have psychosocial support needs were reported to have a lower HRQOL compared with those without. Patients showed a large difference on the social function scale. Emotional function had an even larger difference, but investigators reported that there was not an applicable threshold. Severa, medium differences were reported, including cognitive functioning, fatigue, sleep disturbances, and financial impact.

Hammersen F, Pursche T, Fischer D, Katalinic A, Waldmann A. Psychosocial and family-centered support among breast cancer patients with dependent children. 

. 2021;30(3):361-368. doi:10.1002/pon.5585

Attention needs to be paid to the psychosocial needs of patients, especially those with poor health-related quality of life, who have little support, or are single mothers.

Ariana Pelosci

Articles

Steven J. Chmura, MD, PhD, compares addition of metastases-directed therapy vs SOC alone for oligometastatic breast cancer

Cancer fatalism common among rural residents

FDA grants olaparib priority review in BRCA-mutated HER2-negative high-risk early breast cancer

Consideration towards the psychosocial support needs of patients with breast cancer who have dependent children is imperative