Superior outcomes were observed in men with intermediate-risk prostate cancer who received magnetic resonance (MR)-guided focused ultrasound (MRgFUS) focal therapy than patients in the same population were treated with radical prostatectomy or radiation therapy, demonstrate findings from a phase 2b study (NCT01657942) presented at the 2021 American Urological Association Annual Meeting.

“ExAblate MR-guided focal therapy using real-time MR thermometry preserves urinary incontinence and sexual function and it’s an effective for grade group 2 and 3 prostate cancer cancers are based on 2-year biopsy outcomes,” said lead author Behfar Ehdaie, MD, MS, a urologic surgeon at Memorial Sloan Kettering Cancer Center. “ExAblate MR-guided focus ultrasound may enable men to consider a tissue preserving approach and defer or avoid radical therapy.”

At 24 months, 88% of men had no evidence of grade group 2 or 3 prostate cancer in the treatment area according to targeted prostate biopsy. Additionally, 60% of men had no evidence of grade group 2 or 3 disease anywhere in the prostate gland, including outside of the treatment area. Serum PSA levels decreased by almost 50% after treatment and stabilized after 6 months.

Ehdaie said that men who undergo prostatectomy or radiation therapy often experience significant declines in erectile function and urinary incontinence. Data from a study of 3262 men published in 2020 showed that, at 12 months, about 60% experienced erectile dysfunction following nerve-sparing radical prostatectomy and approximately 50% experienced the same following external beam radiation therapy.

 Men who have intermediate-risk prostate cancer, grade group 2 or 3, are often ineligible for active surveillance or experience early disease progression, up to 40% in findings from the ProtecT trial (NCT02044172), leading to surgery or radiation therapy.

Ehdaie and colleagues explored MRgFUS as an alternative therapy that reduces side effects while maintaining cancer control by targeting areas of no cancer within the prostate gland. He said the ExAblate MR-guided focus ultrasound device delivers targeted high intensity focused ultrasound therapy through the rectum. Ehdaie added that multicenter retrospective studies have shown focal therapy for prostate cancer is safe, and approximately 80% of men require no further prostate cancer-directed treatment.

Investigators evaluated MRgFUS in a single arm, multicenter trial. Men (N = 101) were treated at 7 academic centers and 1 private practice. MRgFUS was delivered focally to the lesion with a margin of normal tissue of greater than or equal to 5 mm based on planning. Treatment was monitored with real-time MR thermometry. Concurrent grade group 1 prostate cancer foci were not treated.

Men with untreated unilateral and more visible, grade group 2 or 3 prostate cancer were eligible. Patients were excluded if they were unable to undergo MRI or had large calcification between the rectum and the planned targeted treatment zone that could interfere with treatment.

Patients underwent targeted and systematic biopsies at 6 and 24 months after treatment, and examinations with quality of life measurements every 3 months.

The primary end points were efficacy and safety. Secondary end points included change in baseline patient-reported quality of life at 24 months.

The average patient age was 63 years and 86% of the cohort was White. The median PSA was 5.7 ng/mL. Eighty-four patients had at least clinical stage T1c disease. Seventy-eight percent of patients were in grade group 2 and 22% were in grade group 3.

Ehdaie said investigators recorded no serious adverse events (AEs). Most minor or moderate AEs self-resolved by 90 days. Two patients had ejaculation disorder and 1 had hematospermia beyond 90 days.

Erectile function scores were slightly worse at 24 months compared with baseline (HR, -3.5; 95% CI, -5.4 to -1.6). Ten (13%) reported no sexual activity and 81% of patients achieved erections adequate for intercourse.

Lower urinary tract symptoms were similar at baseline and 24 months (mean score difference, 1.1; 95% CI, 0.33-1.8).

“Overall, approximately 75% of men were able to achieve functional reactions after treatment at 24 months without starting a new erectile function medication,” Ehadie said. “No patients reported urinary incontinence and the estimated probability of urinary continence over time was excellent.”

Ehadie B, Tempany C, Holland F, et al. MRI-guided focused ultrasound (MRgFUS) focal therapy for intermediate-risk prostate cancer: final results of a phase IIb multicenter study. Presented at: 2021 American Urological Association Annual Meeting; September 10-13, 2021; virtual. Abstract LBA02-12.

Hoffman KE, Penson DF, Zhao Z, et al. Patient-reported outcomes through 5 years for active surveillance, surgery, brachytherapy, or external beam radiation with or without androgen deprivation therapy for localized prostate cancer. 

. 2020;323(2):149-163. doi:10.1001/jama.2019.20675

Hamdy FC, Donovan JL, Lane JA, et al. 10-Year outcomes after monitoring, surgery, or radiotherapy for localized prostate cancer. 

. 2016;375(15):1415-1424. doi: 10.1056/NEJMoa1606220

Guillaumier S, Peters M, Arya M, et al. A multicentre study of 5-year outcomes following focal therapy in treating clinically significant nonmetastatic prostate cancer. 

. 2018;74(4):422-429. doi:10.1016/j.eururo.2018.06.006

Articles

Patients with prostate cancer fared better following treatment with magnetic resonance-guided focused ultrasound focal therapy than with radical prostatectomy or radiation therapy, shows study presented at 2021 AUA Annual Meeting.


 Men with Intermediate-Risk Prostate Cancer Experience Improved Sexual Function, Urinary Continence Following MRgFUS Therapy

Patients with metastatic castration-resistant prostate cancer (mCRPC) who are obese report better disease specific and overall survival (OS) than patients who are overweight or normal weight, indicate findings from an analysis of three phase 3 clinical trials presented at the 2021 American Urological Association Annual Meeting.

“The BMI effect on cancer-specific mortality was also confirmed as a continuous and as a categorical variable,” said study coauthor Giuseppe Ottone Cirulli, MD, a urology resident of Vita-Salute San Raffaele University in Milan, Italy. “Additionally, the protective effect of BMI is not related to the higher dose of chemotherapy.”

Cirulli said that prior data have demonstrated the correlation between BMI and survival outcomes in prostate cancer. In this study, investigators sought to determine whether BMI among patients with mCRPC is associated with OS and disease-specific mortality.

Investigators identified 1577 patients in the ASCENT2 (NCT00273338), MAINSAL (NCT00988208), and VENICE (NCT00519285) trials, 655 of whom had died by the end of the studies. The median follow-up for survivors was 12 months. The Cox semi-proportional hazard model was utilized to predict for OS, while the competing risks regression was utilized to predict for cancer-specific mortality.

There were adjusted analyses for age, prostate-specific antigen, ECOG, number of metastasis, and prior therapy.

The median age was 69 years, and the median BMI was 28 kg/m2. Investigators analyzed the role of BMI on survival outcomes both as a continuous and categorical variable (<20 vs 20-25 vs 25-30 vs >30 km/m2). A BMI of 30 kg/m2 or greater was considered obese.

BMI emerged as a protective factor for OS both as a continuous variable (HR, 0.96; 

= .015) and as a categorical variable (HR, 0.71; 

= .027). Similarly, BMI’s effect on cancer-specific mortality was confirmed both as a continuous (HR, 0.94; 

= .002) and as a categorical variable (HR, 0.65; 

Cirulli and colleagues selected patients from ASCENT2, MAINSAL, and VENICE because all 3 included men with mCRPC treated with docetaxel. Chemotherapy dose is determined in part by weight, but investigators determined there was no interaction between the BMI categories and the docetaxel dose (all 

In ASCENT2, patients were randomly assigned to 45 μg DN-101, 36 mg/m2 docetaxel, and 24 mg dexamethasone weekly for 3 weeks of a 4-week cycle (n = 476) or 5-mg twice-daily prednisone plus 75 mg/m2 of docetaxel and 24 mg dexamethasone every 3 weeks (n = 477).

The median follow-up for patients alive at last assessment was 11.7 months. The median OS was 17.8 months (95% CI, 16.0-19.5) in the experimental arm and 20.2 months (95% CI, 18.8-23.0) in the control arm (log-rank 

 = .002). Survival remained poorer in the experimental arm even after adjusting for baseline variables (HR, 1.33; 

In MAINSAL, chemotherapy-naïve patients with progressive mCRPC were randomized to 75 mg/m2 docetaxel on day 1 and 5 mg twice-daily prednisone on days 1 to 21 and either 25 mg once-daily lenalidomide (n = 533) or once-daily placebo (n = 526) on days 1 to 14 of each 21-day treatment cycle.

The median OS was 17.7 months (95% CI, 14.8-18.8) in the lenalidomide group and was not reached in the placebo group (HR, 1.53; 95% CI, 1.17-2.00; 

= .0017). The trial was subsequently closed early due to futility.

In VENICE, 1224 chemotherapy-naïve patients with adequate organ function were assigned to 75 mg/m2 docetaxel every 3 weeks plus 5 mg twice-daily oral prednisone (5 mg twice daily). They were then randomly allocated to 6 mg/kg of aflibercept (Eylea; n = 612) or placebo (n = 612) every 3 weeks. Results showed that the median OS was 22.1 months (95.6 CI, 20.3-24.1) in the aflibercept group vs 21.2 months (95.6% CI, 19.6-23.8) in the placebo group (HR, 0.94; 95.6% CI, 0.82-1.08; 

Martini A, Cirulli GO, Gandaglia G, et al. The obesity paradox in metastatic castration resistant prostate cancer. Presented at: the 2021 American Urological Association Annual Meeting; September 10-13, 2021; virtual. Abstract PD05-01.

Scher HI, Jia X, Chi K, et al. Randomized, open-label phase III trial of docetaxel plus high-dose calcitriol versus docetaxel plus prednisone for patients with castration-resistant prostate cancer. 

. 2011;29(16):2191-2198. doi:10.1200/JCO.2010.32.8815

Petrylak DP, Vogelzang NJ, Budnik N, et al. Docetaxel and prednisone with or without lenalidomide in chemotherapy-naive patients with metastatic castration-resistant prostate cancer (MAINSAIL): a randomised, double-blind, placebo-controlled phase 3 trial. 

. 2015;16(4):417-425. doi:10.1016/S1470-2045(15)70025-2

Tannock IF, Fizazi K, Ivanov S, et al. Aflibercept versus placebo in combination with docetaxel and prednisone for treatment of men with metastatic castration-resistant prostate cancer (VENICE): a phase 3, double-blind randomised trial. 

. 2013;14(8):760-768. doi:10.1016/S1470-2045(13)70184-0

Obese men are more likely to have improved overall survival following treatment for mCRPC than man who are overweight or normal weight, analysis finds. 

Higher BMI Linked to Superior Survival in mCRPC

Whether they are in a premalignant state of monoclonal B lymphocytosis (MBL), treatment naïve and under surveillance, or undergoing active treatment, patients with chronic lymphocytic leukemia (CLL) are at an increased risk for infection, shared Carsten Utoft Niemann, MD, PhD, in a presentation during the 2021 SOHO Annual Meeting.

With the help of the machine learning–based algorithm CLL Treatment-Infection Model (CLL-TIM), Niemann and his colleagues hope to learn whether the natural history of immune dysfunction and infections in CLL can be changed.

Investigators have made great strides in improving survival for patients with CLL, following the advent of chemoimmunotherapy and targeted therapy approaches. Unfortunately, mortality due to infection in these patients has not changed in 4 decades, Niemann explained, and infections are now the leading cause of death among patients with CLL.

“Looking at patients diagnosed with CLL, [they] tend to have a higher risk of having a serious infection within the first 5 years,” said Niemann, an associate professor, head of the CLL Lab, and chair of the Nordic CLL Study Group, in the Department of Hematology, Rigshospitalet, Copenhagen, Denmark. “The 30-day mortality [rate] upon a serious infection for patient diagnosed with CLL is 10%; the 1-year mortality [rate] is only 11% for patients starting treatment for CLL even though 50% of them will have a serious infection after starting treatment. This means that infections are actually more dangerous for patients with CLL who are untreated.”

Niemann is a coinvestigator in the phase 2 PreVent-ACaLL trial (NCT03868722), in which investigators will use the CLL-TIM algorithm to determine whether short-term treatment with the BTK inhibitor acalabrutinib (Calquence) plus the BCL-2 inhibitor venetoclax (Venclexta) can improve immune function and reduce the risk for infection compared with observation in patients with high-risk, newly diagnosed CLL.

“The aim here by this short 3-month treatment is not to 

 CLL,” he said. “The aim is to reduce the CLL clone back into what we consider monoclonal B lymphocytosis and, at the same time, treat the natural history of CLL and immune dysfunction. Thus, we aim to turn back the CLL into a normal immune function, and the outcome here is actually infection-free, treatment-free survival.”

Twenty-five patients will be randomly assigned to the treatment arm, which will be given in 3 cycles of 28 days, and 25 will be assigned to observation. Enrollment has opened in Denmark and is scheduled to open soon in the Netherlands and Sweden. The primary end point is grade 3 or higher infection-free survival in the treatment arm compared with the observation arm after 24 weeks.

CLL-TIM identifies patients at risk for infection or CLL treatment within 2 years of diagnosis as validated on both internal and external cohorts. The ensemble algorithm incorporates 28 machine learning algorithms based on data collected from 4149 patients with CLL. The model is capable of dealing with heterogeneous data, including high rates of missing data to be expected in the real-world setting, with a precision rate of 72% and a recall rate of 75%.

Niemann added that 6 European nations are collaborating in the CLL-CLUE consortium to assess immune dysfunction and drug sensitivity in primary samples collected from patients and clinical trials, and biobanks. Long term, the goal is to better individualize CLL treatment.

Immune Disfunction Starts Long Before Diagnosis

Niemann said that patients with CLL are more likely to be prescribed macro lights, antibiotics, and/or antivirals as much as 20 years before diagnosis. “This indicates that the immune dysfunction, at least, happens decades prior to diagnosis of CLL,” he added.

Going beyond the patient’s CLL and looking at their entire medical history, Niemann said physicians can see the burden of comorbidity in this population. “Almost all types of comorbidities for patients with CLL will increase the overall mortality and also for most of these comorbidities, will increase the CLL-related mortality,” he said.

That said, it appears both treatment and CLL itself play a role in incidence of infection. Niemann noted that lower respiratory tract infections and urinary tract infections are common for the 6 months of treatment with ibrutinib (Imbruvica). “This may indicate that we have an improvement in immune function and lower degree of infections after the first half year on targeted therapy.”

Niemann pointed out that, outside of clinical trials, close to 50% of patients discontinue ibrutinib by 30 months, many due to infections. Physicians must consider that infections might also affect the continuous treatment of patients, he added.

“On the other hand, [there is] no doubt that we may, for patients who are treated, actually improve the immune function over time,” Niemann said. Patients with less disease burden in terms of being treatment-naïve have a lower risk of infections than patients who are relapsed/refractory and would be expected to have had more aggressive or longer duration of CLL.”

Cumulative mean number of infections are lower in patients whose immune globulin levels increase during ibrutinib treatment. However, Niemann said there is no clear correlation between immunoglobulin deficiency and the risk for infections.

“That is what we’ve been working on predicting the risk of infections or risk of needing treatment for CLL,” he said.

To help the patient in the clinic, Niemann said all patients with CLL may have increased infection risk, but investigators need to identify those who at greatest risk for serious infections. Further, patients with CLL are at risk for both increased frequency of infections and also in the distribution of infections, especially for pneumococcal disease.

“Vaccine responses in CLL are impaired due to immune dysfunction. Thus, it should be encouraged to have early vaccination of patients with CLL, and repeat vaccination during treatment and after treatment,” he said. “Immunoglobulin substitution should only be used for patients who both have low IgG [immunoglobulin G] levels and frequent infections as we cannot clearly define these patients just by measuring the IgG levels.”

Niemann CU. Management of infections in patients with CLL. Presented at: the 2021 SOHO Annual Meeting. Virtual. September 8-13, 2021.

Da Cunha-Bang C, Agius R, Kater AP, et al.PreVent-ACaLL short-term combined acalabrutinib and venetoclax treatment of newly diagnosed patients with CLL at high risk of infection and/or early treatment, who do not fulfil IWCLL treatment criteria for treatment. A randomized study with extensive immune phenotyping. 

. 2019;134(supplement_1):4304. doi:10.1182/blood-2019-121907

Agius R, Brieghel C, Andersen MA, et al. Machine learning can identify newly diagnosed patients with CLL at high risk of infection. 

. 2020;11(1):363. doi:10.1038/s41467-019-14225-8

Patients with chronic lymphocytic leukemia (CLL) are at an increased risk for infection. 

Infection Control a Necessity in Treating CLL

“Smarter screening” strategies may play a crucial role in helping Latina and Black women survive breast cancer at the same rates as their White counterparts, according to a presenter at the 

 School of Nursing Oncology virtual conference.

During her presentation, Olufunmilayo I. Olopade, MD, FACP, OON, American Cancer Society clinical research professor at the University of Chicago’s Center for Clinical Cancer Genetics & Global Health, stressed the need to better understand how breast cancer affects Latina and Black women to improve their survival outcomes following treatment.

“We want to make sure we can provide the right treatment for the right patient at the right time,” explained Olopade. “Then, we can keep our families healthy…what we're looking for in preventive oncology, we can do in the clinic and we can also do it in the population. [We] identify individuals who have already had cancer as a way for us to reach their family members.”

Olopade told the attendees that screening has been an effective tool at reducing breast cancer deaths. However, in her research, Black women in and around the Chicago, Illinois area get screened at rates higher than the national average, yet still have poorer outcomes than White women — even though patients achieve pathologic complete responses at similar rates.

Over time, she said she has learned from genomic assays that breast cancer is not simply one disease but is made up of several different ones. Furthermore, she noted how she has learned that screening for early detection of breast cancer should no longer be age based.

“What we learned from Chicago is that Black and Brown women, and in fact, all young women who get breast cancer under the age of 14, are the ones that are having the worst disparity. In all other cancers, older women tend to do worse,” she said. “We suddenly say, ‘Everyone starts screening at 40,’ [but] there are some women who would have had breast cancer that would have the potential to kill them before they ever get that first mammogram.

“So that’s why we're going away from talking about age-based screening to begin to say, ‘Let us personalize screening.’ Let us all figure out what exactly we are at risk for. Are we at risk for a ‘cheetah’ type of cancer? Or are we at risk for a ‘snail’ type of cancer that grows very slowly?”

Patterns of Inherited Breast Cancer in Black Women

Olopade has studied patterns of inherited breast cancer women in Nigeria, Cameroon, Uganda, Brazil, and among Black women in the United States. Those data, along with findings from the CARRIERS study which included 32,247 women with breast cancer and 32,544 controls, show that 

 are the most important genes for assessing breast cancer risk in this patient population. Black women who harbor these genes develop cancer are almost 15 years younger at diagnosis on average compared with White women who carry the same pathogenic variants.

“These are women who get breast cancer at a very young age. So that’s why we cannot use a one-size-fits-all [approach], and then say, ‘Oh, but you know, 

 are not important.’ They are important. It all depends on your population. When you test 1000 cases and 1000 controls in Nigeria and you have almost 12% of them showing up with a mutation in

, you’re going to focus on that as an intervention for cancer control.”

Determining a patient’s individual risk is challenging, in part because Black women tend to be underrepresented in clinical trials in the United States and abroad. Genomic testing for precision risk assessment will transform cancer care, Olopade said.

“We can’t just take what is being shown in White women and then expect it to work for Indian women, expect it to work for Asian women, expect it to work for women from Africa,” she added. “So, what is the heterogeneity? What is it that we need to do for Black and Brown women?”

This is where investigators need to go beyond race and ethnicity, she said. Physicians can use data from genome-wide association studies (GWAS) to develop a polygenic risk score (PRS), which is calculated for an individual based on the presence or absence of risk variants identified in large GWAS studies. PRS can provide better insight than traditional risk models, especially in these populations. The model can estimate risk for a Black or Brown woman based on the proportion of African ancestry in her DNA.

“We can now identify women who are in the top percentile, [representing] 5% of women who have a risk that is actionable before the age of 50. If we can find those women before the age of 50, or even if we can…can really track them [and] counsel them, and then we can put them on a screening, that is going to be different because they are at risk for [estrogen receptor]-negative breast cancer, [and] I think that will really help the field. We’re talking about deescalating—not just using more and more treatment. We have to deescalate in what we're doing for early detection. We have to use innovations.”

Olopade OI. Retooling precision oncology for true equity of cancer care. Presented at: 5th Annual School of Oncology Nursing; August 6-7, 2021; virtual.

Hu C, Hart SN, Gnanaolivu R, et al. A population-based study of genes previously implicated in breast cancer. 

. 2021;384(5):440-451. doi:10.1056/NEJMoa2005936

This article was originally published on OncLive as, “

Smarter Screening, Risk Assessments Are Key to Eliminating Racial Disparities in Breast Cancer Outcomes

“We want to make sure we can provide the right treatment for the right patient at the right time,” says Olufunmilayo I. Olopade, MD, FACP, OON. 

 Personalized Screenings are Needed to Address Racial Disparities in Breast Cancer Outcomes 

A coalition of professional organizations issued a joint statement on Monday imploring health care employers to require COVID-19 vaccinations for their employees. More than 50 professional health care organizations signed the statement, including the American Society of Hematology (ASH), the American Society of Clinical Oncology, the American Society for Radiation Oncology, the Society for Gynecologic Oncology, and the American Medical Association.

The groups said their endorsement of mandatory COVID-19 vaccination “aims to protect the safety of patients and residents of long-term care facilities,” according to a news release issued by ASH. They hope to establish the health care sector a leader in COVID-19 vaccination.

If implemented, this mandate would cover 17 million health care workers.

“Health care workers have an ethical duty to put patients’ health and well-being first. and getting vaccinated for COVID-19 is integral to that duty,” Ezekiel J. Emanuel, MD, PhD, said in a statement, which he organized. Emanuel is vice provost for global initiatives at the University of Pennsylvania. He is also a breast oncologist, the Diane v.S. Levy and Robert M. Levy University Professor at University of Pennsylvania and co-director of the school’s Health Transformation Institute. He formerly served as special advisor for health policy to the director of the Office of Management and Budget in the White House for the Obama Administration and chair of the Department of Bioethics at the National Institutes of Health for 14 years.

“Employer vaccine mandates are effective and lifesaving, and they are especially appropriate in health care and long-term care settings,” Emanuel added. “No patient should have to worry that they could become infected by one of their care providers, and no provider should put their patient at risk.”

The statement comes as COVID-19 diagnoses, hospitalizations, and deaths are on the rise, mostly among the unvaccinated. Health care workers are more likely to be fully vaccinated than the general population. However, approximately one-quarter of hospital workers who have direct contact with patients had not received a single dose of a COVID-19 vaccine as of the end of May 2021, according to a WebMD and Medscape Medical News analysis of data collected by the Department of Health and Human Services from 2500 hospitals across the United States.

Vaccine administration peaked in late March and early April. The spread of the delta variant, which is more contagious than the alpha variant and resistant to vaccination, has also given new life to a pandemic that seemed to be winding down.

“As the number of cases, hospitalizations and deaths continue to rise due to the COVID-19 delta variant, especially among unvaccinated persons, requiring that all health care workers who can get vaccinated receive a COVID-19 vaccine will help protect them, their patients, loved ones and others who are vulnerable and immunocompromised,” George M. Abraham, MD, MPH, president of the American College of Physicians, said in the statement.

CDC director Rochelle Walensky, MD, has said that as many as 99% of COVID-19 deaths over the past 6 months have been among those who are unvaccinated.

The Alabama Department of Public Health issued a report July 13 saying that the state had recorded 529 COVID-19 deaths since April 1.

 Of those, 509 were unvaccinated. As of July 16, only 33.6% of the state’s total population and 42.3% of the adult population was fully vaccinated.

The Johns Hopkins Coronavirus Resource Center has recorded 20,733 new cases and 147 new deaths in Alabama over the past 30 days.

In contrast, Vermont leads the nation with more than 68% of the total population fully vaccinated. There have been 3 COVID-19 deaths over the past 30 days, down from a high of 67 in December 2020.

Major health care professional organizations call for covid-19 vaccine mandates for all health workers. News release. July 26, 2021. Accessed July 26, 2021. https://bit.ly/3BFUHwJ

Goodman B, Miller A. Huge number of hospital workers still unvaccinated. WebMD Health News. June 28, 2021. Accessed July 26, 2021. https://wb.md/2UIjOi1

Lopez Bernal J, Andrews N, et al. Effectiveness of Covid-19 vaccines against the B.1.617.2 (Delta) variant. 

. Published online ahead of print July 21, 2021. doi:10.1056/NEJMoa2108891

Alabama Public Health. Unvaccinated people represent 96.2 percent of COVID-19 deaths in Alabama since April 1. July 13, 2021. Accessed July 26, 2021. https://bit.ly/3iOsrPN

US Department of Health and Human Services. COVID-19 Community Profile Report. Alabama state synopsis. July 16, 2021. Accessed July 26, 2021. https://bit.ly/376WBs0

Johns Hopkins University of Medicine Coronavirus Resource Center. Alabama. Accessed July 26, 2021. https://bit.ly/3BTsUZY

Johns Hopkins University of Medicine Coronavirus Resource Center. Vermont. Accessed July 26, 2021. https://bit.ly/3f0yGip

This article was originally published on OncLive as 

“Cancer Organizations Call for Mandated COVID-19 Vaccines for Health Care Workers”

Several cancer organizations signed a group statement calling for health care employers to mandate COVID-19 vaccinations for their employees.  

Cancer Organizations Implore Health Care Employers to Mandate COVID-19 Vaccines 

Post-treatment care for breast cancer survivors must be personalized to address each survivor’s unique experiences, according to a study presented at the ESMO Breast Cancer Virtual Congress 2021. Women in the low- and intermediate-burden subgroups had symptom scores better or equal to the average Dutch woman but many in the high-burden subgroup were significantly worse than average for all 11 symptoms evaluated.

The low subgroup reported a lower symptom burden compared to the general population. The intermediate subgroup experienced burden similar to the general population, although scores for fatigue, insomnia, and cognitive symptoms were slightly worse.

Symptom burden in the high subgroup was significantly than the general population. Compared with the intermediate subgroup, patients in the high burden group were more likely to have at least 1 comorbidity (relative risk ratio (RRR), 2.75; 95% CI, 1.22-6.19; 

 = .015) and more likely to have multiple comorbidities (RRR, 9.19; 95% CI; 3.70-22.8; 

“I was pleasantly surprised to find that so many survivors were doing as well or even better than the average Dutch woman,” lead author Kelly de Ligt, PhD, from the Netherlands Cancer Institute in Amsterdam, said in a news release.

de Ligt added that the findings in the high-burden subgroup were alarming. “This was the smallest group, only 15% of our population, but nonetheless, 1 in 6 women in our study had worse scores than the general population for all symptoms. The differences, ranging between 15 and 20 percentage points, were large enough to be considered not just statistically significant, but clinically relevant as well.”

More and more women are living longer following a diagnosis of breast cancer. The 10-year survival rate is greater than 70% in Europe and 84% for non-metastatic invasive disease in the United States.

 Quality of life is extremely important for these patients and de Ligt said these findings confirm the necessity for personalized approaches to the follow-up of cancer patients, some of whom still require special attention as long as 5 years after diagnosis.

de Ligt and her colleagues surveyed 404 women who received surgery with or without adjuvant treatment for stage I to III breast cancer selected from the Netherlands Cancer Registry. Participants were 1 to 5 years postdiagnosis and compared with a representative sample of 1300 women from the general population.

Investigators assessed participants for fatigue, nausea, pain, dyspnea, insomnia, appetite, constipation, diarrhea, financial burden, and emotional and cognitive symptoms on a scale 0-100 through the EORTC-QLQ-C30. Participants were then segregated into low- (28.7%), intermediate- (55.4%), and high-burden groups (14.6%) based on their responses.

de Ligt and her team also determined that patients with comorbidities such as heart disease and diabetes were more likely to experience a high symptom burden. de Ligt said the association was so strong that investigators could not connect the level of symptom burden with the type of therapy received.

“Future research should attempt to measure patients’ health-related quality of life through Patient Reported Outcome Measures (PROMs) before the start of treatment for breast cancer and afterwards to allow us to measure the effect of the therapy,” she said.

de Light KM, de Rooij BH, Walraven I, et al. Towards tailored follow-up care for breast cancer survivors: cluster analyses based on symptom burden. Presented at: ESMO Breast Cancer Virtual Congress 2021. Abst # 134P_PR. 

Cardoso F, Kyriakides S, Ohno S, et al. Early breast cancer: ESMO clinical practice guidelines for diagnosis, treatment and follow up. 

Breast cancer: statistics. Cancer.net. January 2021. Accessed May 4, 2021. https://www.cancer.net/cancer-types/breast-cancer/statistics

This article was originally published on OncLive as, "

Breast Cancer Survivors Need More Tailored Follow-Up Care

Each patient with breast cancer has a unique experience. Their survivorship care should reflect that.

Tailored Survivorship Care Is Needed in the Breast Cancer Space

PARP inhibitors and novel combinations targeting the androgen receptor (AR) will help define the future treatment paradigm for patients with metastatic castration-resistant prostate cancer (mCRPC), according to William Kevin Kelly, DO.

Investigators have identified molecular changes that occur when a patient’s disease progresses from a castration-sensitive state to a castration-resistant state, which has helped drive advances in therapeutic options, Kelly said in a presentation during the New York GU™ 

 Interdisciplinary Prostate Cancer Congress® and Other Genitourinary Malignancies conference.

“This gave opportunities for investigators to look at these pathways and develop new targets for these alterations,” said Kelly, a professor of medical oncology and urology at Thomas Jefferson University and director of the Division of the Solid Tumor Oncology at Sidney Kimmel Cancer Center at Jefferson Health, both in Philadelphia.

Study findings have shown that the frequency of DNA repair alterations increases as prostate cancer progresses; an estimated 19% to 23% of patients with mCRPC harbor mutations in this pathway, Kelly said.

PARP inhibitors, which target aberrant DNA repair mechanisms, entered the treatment landscape for last year when the FDA approved 2 agents for patients with mCRPC within less than a week.

 On May 15, 2020, rucaparib (Rubraca) became the first biomarker-driven targeted therapy for the malignancy when the FDA granted an accelerated approval for its use in patients with 

-mutant mCRPC (germline and/or somatic) who received prior AR-directed therapy and taxane-based chemotherapy.

Rucaparib was approved based on findings from the single-arm phase 2 TRITON2 trial (NCT02952534), in which monotherapy with the PARP inhibitor resulted in a confirmed objective response rate (ORR) of 43.5% (95% CI, 31.0%-56.7%) by independent review, with 7 (11.3%) complete responses and 20 (32.3%) partial responses. The confirmed ORR by investigator assessment was 50.8% (95% CI, 38.1%-63.4%).

Final approval for rucaparib is contingent on the results of the phase 3 TRITON3 trial (NCT02975934), which is seeking to recruit 400 patients with mCRPC harboring a 

 mutation that has progressed after 1 prior line of therapy with a next-generation AR-targeting therapy.

Four days after rucaparib was approved, olaparib (Lynparza) gained a new indication for treating patients with deleterious or suspected deleterious germline or somatic mutations in homologous recombination repair (HRR) genes including 

 who have progressed following treatment with enzalutamide (Xtandi) or abiraterone acetate (Zytiga) based on findings from the phase 3 PROfound trial (NCT02987543).

In PROfound, investigators determined that olaparib monotherapy was superior to prednisone plus either enzalutamide or abiraterone for patients with mCRPC who had tumors with at least 1 alteration in 

 (cohort A) or in any of 12 HRR genes (cohort B). The study population included 387 patients who had disease progression on prior hormone-targeting agents.

In cohort A, the median radiological progression-free survival (rPFS), the primary endpoint of the study, was 7.4 months (95% CI, 6.2-9.3) for those who received olaparib vs 3.6 months (95% CI, 1.9-3.7) for those who had physician’s choice of standard therapy, which translated into a 66% reduction in the risk of disease progression or death (HR, 0.34; 95% CI, 0.25-0.47; 

 <.0001). In cohort A plus B, median rPFS was 5.8 months for olaparib (95% CI, 5.5-7.4) vs 3.5 months (95% CI, 2.2-3.7), resulting in an HR of 0.49 (95% CI, 0.38-0.63; 

Olaparib also demonstrated an improvement in median OS. In cohort A, the median OS was 19.1 months (95% CI, 17.4-23.4) with olaparib vs 14.7 months (95%CI, 11.9-18.8) for physician’s choice of therapy (HR, 0.69; 0.50-0.97; 

 = .02). In cohorts A plus B, the median OS was 17.3 months (95% CI, 15.5-18.6) vs 14.0 months (95% CI, 11.5-17.1), translating into an HR of 0.79 (95% CI, 0.51-1.03).

Kelly added that new data presented at the 2021 Genitourinary Cancers Symposium showed that patients with 

 mutations also exhibit significant response to olaparib.6 “Those are another subset of patients that we need to understand and possibly treat in the future,” he said.

In addition to PARP inhibitor studies, the treatment landscape is being shaped by trials that explore therapies in combination or in sequence. “Therapeutic options for mCRPC have greatly expanded over the years,” Kelly said. “So, really, the question is, What comes next? How do we actually pick the order [of treatments]? Or are there better combinations?”

Of note, the efficacy of cabazitaxel (Jevtana), a taxane chemotherapy, was established in the setting of recurrent mCRPC in the phase 4 CARD trial (NCT02485691) in patients who had previously received docetaxel and progressed within 1 year of receiving either enzalutamide or abiraterone. Participants were randomized to receive cabazitaxel plus prednisone and granulocyte colony-stimulating factor vs abiraterone plus prednisone or enzalutamide.

Patients who received cabazitaxel had a median imaging-based progression-free survival of 8.0 months (95% CI, 5.7-9.2) vs 3.7 months (95% CI, 2.8-5.1) for those who received an antiandrogen (HR, 0.54; 95% CI, 0.40-0.73; 

 <.001). The secondary end point of median OS was 13.6 months (95% CI, 11.5-17.5) with cabazitaxel versus 11.0 months (95% CI, 9.2-12.9) with either antiandrogen (HR, 0.64; 95% CI, 0.46-0.89; 

“The quality-of-life measures were better all the way through with cabazitaxel versus another AR-directly therapy,” Kelly added. “Pain response was significantly better with the use of cabazitaxel, 45.0% vs 19.3%. Probability of no pain progression was also improved with chemotherapy vs abiraterone or enzalutamide, which really starts defining that chemotherapy still has a role in patients with mCRPC.”

In the phase 3 ACIS trial (NCT02257736), investigators found that adding apalutamide (Erleada), an AR inhibitor, to abiraterone plus prednisone reduced the risk of radiographic progression or death by 30% in patients with chemotherapy-naïve mCRPC receiving androgen deprivation therapy (ADT).

At a median follow-up of 54.8 months, the median rPFS was 24.0 months in the apalutamide arm compared with 16.6 months with placebo plus abiraterone and prednisone (HR, 0.70; 95% CI, 0.60-0.83). OS in the combination arm was 36.2 versus 33.7 months in the control arm (HR, 0.95; 95% CI, 0.81-1.11; 

The findings met the primary end point of the study, but did not significantly improve OS, Kelly noted. He said subgroup analyses may provide further information about which patients could benefit from the approach.

“There are multiple other opportunities for AR-targeted therapies,” Kelly said. “There's multiple new agents that are going to be reporting out that look at different targets from EZH2 to BET inhibitors to transcription coactivators such as CBP and p300, inhibitors that are unique actions and we look forward to those trials coming out.”

Kelly WK. New approaches for advanced CRPC: hormonal agents and PARP inhibitors. Presented at: New York GU™ 

 Interdisciplinary Prostate Cancer Congress® and Other Genitourinary Malignancies; March 12-13, 2021; Virtual.

Hematology/oncology (cancer) approvals & safety notifications. FDA. Updated March 10, 2021. Accessed March 15, 2021. 

Abida W, Patnaik A, Campbell D, et al. Rucaparib in men with metastatic castration-resistant prostate cancer harboring a BRCA1 or BRCA2 gene alteration. 

. 2020;38(32):3763-3772. doi:10.1200/JCO.20.01035

Lynparza. Prescribing information. AstraZeneca; 2020. Accessed March 15, 2021.

Hussain M, Mateo J, Fizazi K, et al; PROfound Trial Investigators. 

. 2020;383(24):2345-2357. doi:10.1056/NEJMoa2022485

De Bono JS, Matsubara N, Penel N, et al. Exploratory gene-by-gene analysis of olaparib in patients (pts) with metastatic castration-resistant prostate cancer (mCRPC): PROfound. 

. 2021;39(suppl 6):126. doi:10.1200/JCO.2021.39.6_suppl.126

de Wit R, de Bono J, Sternberg, CN, et al; CARD Investigators. Cabazitaxel versus abiraterone or enzalutamide in metastatic prostate cancer. 

. 2019;381(26):2506-2518. doi:10.1056/NEJMoa1911206

Rathkopf DE, Efstathiou E, Attard G, et al; ACIS investigators. Final results from ACIS, a randomized, placebo (PBO)-controlled double-blind phase 3 study of apalutamide (APA) and abiraterone acetate plus prednisone (AAP) versus AAP in patients (pts) with chemo-naive metastatic castration-resistant prostate cancer (mCRPC). 

. 2021;39(suppl 6):9. doi:10.1200/JCO.2021.39.6_suppl.9

This article originally appeared on OncLive as, "

PARP Inhibitors, Novel Combos Represent the Future in Metastatic CRPC

PARP inhibitors and novel combinations targeting the androgen receptor will help define the future treatment paradigm for patients with metastatic castration-resistant prostate cancer.

What's Next in mCRPC Treatment? Expert Weighs In

Treatment with chimeric antigen receptor (CAR) T cells has induced unprecedented overall response rates (ORR) and complete response (CR) rates in patients with relapsed/refractory B cell malignancies. However, up to 50% of patients will relapse.1

 International Congress on Hematologic Malignancies, David B. Miklos, MD, PhD, associate professor of medicine (blood and marrow transplantation) at the Stanford University Medical Center, suggested that CAR agents targeting multiple antigens might hold the key to breaking through that resistance.

Previous studies have established several factors associated with relapse following CAR T therapy, including loss of the CD19 antigen and aberration in the CD58 antigen, which helps to activate engineered T cells and assists in killing cancer cells.

In a presentation at the 2018 American Society of Hematology Annual Meeting, Jean Oak, PhD, and colleagues found that 8 of 22 (36%) of patients with refractory B cell lymphomas who did not respond to treatment with axicabtagene ciloleucel (Axi-cel) or relapsed after day 28. Five patients (62%) who failed therapy had loss or downregulation of CD19, suggesting that single target antigen loss is a common mechanism of CAR T failure.2

Majzner et al analyzed CD58 status in 51 patients who were treated with axicabtagene ciloleucel for relapsed/refractory B cell lymphomas. Twelve (24%) patients had CD58 mutation or lack of expression, and 11 of those 12 had progressive disease.3

Up to 50% of patients with B-cell malignancies will relapse on CAR T-cell therapy. Investigators are looking in to new ways to overcome that drug resistance.

Jason Harris