While cabozantinib (Cabometyx) exposure was not a predictor of progression-free survival, it was related to high rate of palmar-plantar plantar erythrodysesthesia (PPE) and diarrhea in patients with advanced renal cell carcinoma (RCC) who are given frontline cabozantinib plus nivolumab (Opdivo). These findings, which were a part of an exposure-response analysis of the phase 3 CheckMate 9ER trial, were presented during the 2021 ASCO Annual Meeting.

“ER modeling predicts that appropriate dose modification of the 40-mg cabozantinib starting dose to manage AEs [adverse effects] will not adversely affect the efficacy of nivolumab plus cabozantinib in first-line advanced RCC,” lead study author Amishi Y. Shah, MD, an assistant professor in the Department of Genitourinary Medical Oncology at The University of Texas MD Anderson Cancer Center, and co-authors wrote in a poster of the data.

The CheckMate 9ER trial revealed that the frontline combination of nivolumab plus cabozantinib significantly improved PFS (HR, 0.51; 95% CI, 0.41-0.64; 

 < .001), overall survival (OS; HR, 0.60; 95% CI, 0.40-0.89; 

 < .001) compared with sunitinib (Sutent) in patients with advanced RCC.

In the study, patients with previously untreated RCC received 40 mg of cabozantinib daily in combination with 240 mg of nivolumab every 2 weeks.

The regimen was generally well tolerated among patients, with low rates of treatment-related discontinuations. Dose modifications appeared to successfully manage AEs and allow patients to tolerate the regimen.

Patients (n = 320) received a median average daily dose of 29.4 mg of cabozantinib in the CheckMate 9ER trial. First-level dose reductions of cabozantinib to 20 mg daily because of AEs were observed in 50% (n = 161) of patients after a median time of 98 days (range, 9-506). Second-level dose reductions of cabozantinib to 20 mg every 2 days were observed in 8.1% of patients (n = 26) after a median time of 173 days (range, 65-613).

Because of AEs, 7.5% of patients (n = 24) discontinued cabozantinib, 6.6% of patients (n = 21) discontinued nivolumab, and 5.6% of patients (n = 18) discontinued both agents.

With a database lock date of March 30, 2020, investigators sought to understand the relationship between cabozantinib exposure, and the efficacy and safety outcomes observed in the CheckMate 9ER trial utilizing time-to-event Cox proportional hazard ER models.

The models evaluated specified end points, including PFS, dose modifications (holds or reductions), and select AEs, such as grade 1 or greater PPE, grade 3 or greater diarrhea, grade 3 or greater hypertension, grade 3 or greater fatigue/asthenia, and grade 3 or greater alanine aminotransferase (ALT)/aspartate aminotransferase (AST) increase.

“Cabozantinib exposure was defined as the overall average concentration from time zero to time of event or censoring [CAVG0T] for each end point and estimated by population pharmacokinetic modeling,” Shah and co-authors wrote.

As of the database lock date, survival data were immature, so the relationship between OS and cabozantinib exposure was not assessed.

Regarding end points, the number of patients at risk receiving 1 or more doses of cabozantinib were 311 for PFS, 318 for dose modification, 320 each for PPE, diarrhea, hypertension, and fatigue/asthenia, and 317 for ALT/AST elevation. Of these, the number of patients with 1 or more measurable cabozantinib concentration was 303 for PFS, 306 for dose modification, 308 each for PPE, diarrhea, hypertension, and fatigue/asthenia, and 307 for ALT/AST elevation.

Regarding the number of events by end point, the number of patients receiving at least 1 dose of cabozantinib was 144 for PFS, 285 for dose modification, 128 for PPE, 22 for diarrhea, 44 for hypertension, 24 for fatigue/asthenia, and 35 for ALT/AST elevation. Of these, patients with at least 1 measurable cabozantinib concentration included 139 for PFS, 279 for dose modification, 128 for PPE, 21 for diarrhea, 44 for hypertension, 23 for fatigue/asthenia, and 34 for ALT/AST elevation.

In evaluable populations, patients were a median age of 62 years (range, 29-90), with a median body weight of 80.3 kg (range, 36.0-159.3), and the majority of patients (77%) were male with high Karnofsky Performance Statuses (≥90, 79%) and low lactase dehydrogenase (≤1.5 x upper limit of normal, 94%). The median nivolumab clearance was 0.009 L/h (range, 16.0-53.4).

The target lesions were a median of 69 mm (range, 10-330). Most patients did not have prior radiotherapy (86%) but underwent prior nephrectomy (69%).

Most patients (65%) were randomized to treatment in the CheckMate 9ER trial less than 1 year from initial diagnosis.

The majority of patients (74%) had a baseline PD-L1 status of less than 1% or an indeterminate status and International Metastatic RCC Database Consortium (IMDC) scores of 1 or 2 (58%).

In the PFS analysis population (n = 303), more favorable IMDC scores were observed in patients in higher exposure quartiles. However, baseline characteristics were generally similar otherwise.

Further results revealed that cabozantinib exhibited higher interpatient variability in apparent clearance (n = 306; median 1.93 L/h; range, 0.64-10.3) and average exposure (n = 303; median 564.6 ng/mL; range, 29.3-1995).

With regard to PFS, the median exposure in quartile 4 was 848.1 ng/mL (HR relative to CAVG0T, 1.00; 95% CI, 1.00-1.00). Comparatively, the median exposure was 302.3 ng/mL (HR, 0.99; 95% CI, 0.71-1.40) in quartile 1, 485 ng/mL (HR, 1.00; 95% CI, 0.79-1.25) in quartile 2, and 641.2 ng/mL (HR, 1.00; 95% CI, 0.88-1.14) in quartile 3. Overall, this suggested that PFS was not different between cabozantinib exposure quartiles.

Regarding the development of grade 1 or greater PPE, the median exposure in quartile 4 was 872.1 ng/mL (HR relative to CAVG0T, 1.00; 95% CI, 1.00-1.00). Comparatively, the median exposure was 318.9 ng/mL (HR, 0.51; 95% CI, 0.37-0.70) in quartile 1, 512.5 ng/mL (HR, 0.65; 95% CI, 0.53-0.80) in quartile 2, and 658.6 ng/mL (HR, 0.77; 95% CI, 0.68-0.87) in quartile 3.

Regarding the development of grade 3 or higher diarrhea, the median exposure in quartile 4 was 825.1 ng/mL (HR relative to CAVG0T, 1.00; 95% CI, 1.00-1.00). Comparatively, the median exposure was 312.2 ng/mL (HR, 0.38; 95% CI, 0.19-0.75) in quartile 1, 471.2 ng/mL (HR, 0.51; 95% CI, 0.32-0.82) in quartile 2, and 606.9 ng/mL (HR, 0.66; 95% CI, 0.49-0.88) in quartile 3.

“The risk of developing PPE or diarrhea was greater at higher cabozantinib exposure quartiles; there was not association for hypertension, fatigue/asthenia, or AST/ALT elevation,” wrote Shah and co-authors.

Regarding dose modifications, the median exposure was 2.96 L/h in clearance quartile 4 (HR relative to CL/F, 1.00; 95% CI, 1.00-1.00). Comparatively, the median exposure was 1.32 L/h (HR, 1.20; 95% CI, 0.91-1.57) in quartile 1, 1.74 L/h (HR, 1.13; 95% CI, 0.94-1.35) in quartile 2, and 2.19 L/h (HR, 1.07; 95% CI, 0.97-1.18) in quartile 3.

“The risk of cabozantinib dose modification increased with decreasing cabozantinib clearance but was not significantly different between cabozantinib clearance quartiles,” Shah and co-authors wrote.

Additionally, cabozantinib exposure was not found to be a statistically significant predictor of PFS, and the rate of progression or death was not significantly associated with daily cabozantinib exposure (20 mg vs 40 mg). CAVG0T was 386 ng/mL at the 20 mg daily dose vs 772 ng/mL at the 40 mg daily dose (HR, 1.00; 95% CI, 0.78-1.27).

Increased cabozantinib exposure was significantly associated with an increased risk of PPE (HR, 0.63; 95% CI, 0.50-0.78) and diarrhea (HR, 0.48; 95% CI, 0.29-0.80), but no significant exposure-response relationships were identified for hypertension, fatigue/asthenia, or ALT/AST elevation.

Although not statistically significant, higher cabozantinib clearance was associated with a lower rate of cabozantinib dose modification (2.2 L/h vs 1.2 L/h; HR, 0.87; 95% CI, 0.71-1.07; 3.2 L/h vs 1.2 L/h; HR, 0.80; 95% CI, 0.57-1.12).

A multivariable analysis with backward elimination showed that certain baseline patient characteristics, including sex, nivolumab clearance, and baseline albumin, were significant covariates. Patients with higher baseline nivolumab clearance or lower baseline albumin levels were predicted to have higher rates of disease progression or death.

Shah AY, Motzer RJ, Apolo AB, et al. Cabozantinib exposure-response analysis for the phase 3 CheckMate 9ER trial of nivolumab plus cabozantinib versus sunitinib in first-line advanced renal cell carcinoma. 

 2021;39(suppl 15):4561. doi:10.1200/JCO.2021.39.15_suppl.4561

Articles

While cabozantinib exposure was not a predictor of progression-free survival, it was related to high rate of palmar-plantar plantar erythrodysesthesia  and diarrhea in patients with advanced renal cell carcinoma who are given frontline cabozantinib plus nivolumab. 

Cabozantinib Associated With Higher Rates of Certain AEs in Advanced Kidney Cancer

Men with asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer (mCRPC) who are being treated with radium-223 (Xofigo) plus enzalutamide (Xtandi) can reduce their risk of fractures with the use of bone-protecting agents (BPAs), according to findings presented at the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.1

“This safety analysis confirms the importance to give a bone-protecting agent when treating patients with CRPC and bone metastases,” Silke Gillessen, MD, Oncology Institute of Southern Switzerland, said during a presentation of the safety analysis.

In the randomized phase 3 EORTC-1333-GUCG/Peace-3 trial (NCT02194842), investigators randomized patients 1:1 to receive either enzalutamide at 160 mg daily plus radium-223 at 55 kBq/kg every 4 weeks for 6 cycles, or enzalutamide alone.

The study population included patients with bone-predominant mCRPC (≥2 bone metastases); asymptomatic or mildly asymptomatic disease; a WHO performance score of 0 or 1; no prior treatment with cyp17 inhibitors, enzalutamide, other radionucleotides, or hemibody radiotherapy; and no known brain or visceral metastases.

Radiographic progression-free survival served as the primary end point.

Following results of fractures occurring in the ERA223 trial (NCT02043678),2 the investigators of the EORTC-1333-GUCG/PEACE-3 trial decided to send out an urgent safety letter. “In this, it was made mandatory to use a bone-protecting agent in all patients for at least 6 weeks before starting radium-223. In April 2018, an IDMC analysis was done, and the recommendation was to continue the trial, but to use a bone-protecting agent in all patients from both arms,” explained Gillessen. “The IDMC is regularly monitoring the trial, and after the review in December last year, recommended to present the updated numbers regarding bone fractures to the scientific community.”

In her presentation at the 2021 ASCO Annual Meeting, Gillessen offered updated results of the safety analysis from the trial, highlighting the impact of BPAs on fracture rates.

As of the April 2021 cut-off, of the 267 patients randomized to both treatment arms, 74 in each were given BPAs.

Before administering the safety letter, 45.2% of patients had not received a BPA, compared with just 3% who had not after the letter was sent out.

The cumulative incidence of fractures at 1 year was 37.1% (95% CI, 21.3%-53.0%) in the combination arm and 15.6% (95% CI, 5.6%-30.3%) in the enzalutamide alone arm. In men who received a BPA, the 1-year incidence of fractures was reduced to 2.7% (95% CI, 0.5%-8.5%) and 2.6% (95% CI, 0.5%-8.3%), respectively.

At 18 months, the cumulative incidence was 45.9% (95% CI, 28.6%-61.6%) in the combination arm and 21.9% (95% CI, 9.5%-37.5%) in the enzalutamide alone arm, without a BPA. With a BPA, the incidence was 4.3% (95% CI, 1.1%-10.9%) and 2.6% (95% CI, 0.5%-8.3%), respectively.

“According to our study, we will continue and want to motivate all investigators to include [bone-protecting agents in the treatment of] patients. And hopefully, we can still report efficacy results as well. Importantly, the IDMC will also continue to closely monitor the study,” Gillessen said.

Radium-223 is an alpha-emitting radiopharmaceutical that has demonstrated an overall survival benefit in men with mCRPC, with the hypothesis that combining it with a novel androgen receptor (AR) pathway inhibitor could improve clinical outcomes.

In the randomized, double-blind, placebo-controlled ERA223 trial, investigators evaluated the use of concurrent treatment with abiraterone acetate (Zytiga; 1000 mg once daily) plus prednisone (5 mg twice daily) or prednisolone (5 mg twice daily) and radium-223 (55 kBq/kg) in 806 patients with mCRPC.2 Symptomatic skeletal event-free survival served as the primary end point.

BPAs were only permitted in the trial if a patient was receiving them at baseline. Initiation of such agents during the study was prohibited to prevent confounding effects. Therefore, only 60% of patients had not received a BPA at study entry.

In a posthoc analysis of the trial, BPAs significantly reduced the rate of fractures in both treatment arms.

“To better understand the nature of these fractures, an independent review of the fracture events was performed. Interestingly, the maturity of fractures in both groups occurred at sites with no detectable metastasis and were considered osteoporotic or traumatic,” Gillessen explained.

“Treatment with [androgen-deprivation therapy (ADT)] can induce bone loss. And we know that bone-protecting agents can be used in this bone loss and also in osteoporotic fractures in men treated with ADT,” Gillessen said. “Bone protecting agents can also delay the time to a first skeletal-related event [SRE] in men with castration-resistant prostate cancer and bone metastasis.”

Skeletal complications may be common in patients with advanced prostate cancer and result in 2 distinct mechanisms, she added: frailty, or osteoporotic fractures are reported in 11% of patients and SREs occur in up to 40% of those treated with ADT and an AR pathway inhibitor.

“To prevent these SREs, many guidelines recommend using bone-protecting agents for patients with castration-resistant prostate cancer and bone metastasis. Combining gamma radiation and hormonal manipulation is a well validated treatment strategy in prostate cancer,” Gillessen said.

1. Gillessen S, Choudhury A, Rodriguez-Vida A, et al. Decreased fracture rate by mandating bone protecting agents in the EORTC 1333/PEACEIII trial combining Ra223 with enzalutamide versus enzalutamide alone: An updated safety analysis. 

. 2021;39:(suppl 15; abstr 5002). doi: 10.1200/JCO.2021.39.15_suppl.5002.

2. Smith M, Parker C, Saad F, et al. Addition of radium-223 to abiraterone acetate and prednisone or prednisolone in patients with castration-resistant prostate cancer and bone metastases (ERA 223): a randomised, double-blind, placebo-controlled, phase 3 trial. 

Men with asymptomatic or mildly symptomatic metastatic castration-resistant prostate cancer who are being treated with radium-223 (Xofigo) plus enzalutamide (Xtandi) can reduce their risk of fractures with the use of bone-protecting agents.

Bone-Protecting Agents Reduce Fracture Risk During Prostate Cancer Treatment

Screenings for breast cancer, colorectal cancer (CRC), and prostate cancer declined sharply from March to May 2020 vs the same time span in 2019, suggesting that public health efforts, such as increased use of screening modalities that do not require a procedure, are needed to address the deficit caused by the COVID-19 pandemic, according to findings from a study that were published in 

Within the 3-month period in 2020, the sharpest decline in screening for breast cancer, CRC, and prostate cancer was observed in April 2020 compared with the same month in 2019; screenings declined by 90.8%, 79.3%, and 63.4% in breast cancer, CRC, and prostate cancer, respectively.

Compared with April 2019, the incidence of breast cancer screenings in April 2020 declined from 4287 per 100,000 individuals (95% CI, 4258-4316) to 394 per 100,000 individuals (95% CI, 385-403). The incidence of CRC screenings declined from 2073 per 100,000 individuals (95% CI, 2058-2087) to 430 per 100,000 individuals (95% CI, 423-436). The incidence of prostate cancer screenings declined from 4025 per 100,000 individuals (95% CI, 3993-4057) to 1474 per 100,000 individuals (95% CI, 1454-1493).

Notably, near complete recovery in monthly screening rates were observed by July 2020 for patients with breast cancer and prostate cancer.

"Unfortunately, by causing cancellations of appointments and cancer screenings, COVID will indirectly cause an increase in cancer deaths—another negative consequence of COVID that has not yet received much public attention," said lead study author Ronald C. Chen, MD, MPH, the Joe and Jean Brandmeyer Endowed Chair in the Department of Radiation Oncology at the University of Kansas Medical Center.

The COVID-19 pandemic significantly affected all elements of health care, including cancer treatment and screening, across the United States in 2020, Chen and co-authors wrote.1 Stay-at-home orders and safety guidelines issued by the CDC to minimize COVID-19 transmission resulted in a significant decline in non-emergency clinical visits, particularly among older, high-risk patients, explained Chen and co-authors.

The study evaluated 3 distinct cohorts of patients from the HealthCore Integrated Research Database, which comprises single-payer administrative claims data and enrollment information from about 60 million patients in Medicare Advantage and commercial insurance plans across the United States. The cohorts included women with breast cancer, men and women with CRC, and men with prostate cancer.

Cancer screenings were evaluated from 2018 to 2020. Evaluable individuals for breast cancer screening or CRC screening were aged 50 to 79 years, and evaluable individuals for prostate cancer screening were aged 50 to 69 years. Individuals had to have at least 2 years of continuous enrollment before the first day of the index month. Restrictions based on medical claims and personal history codes for cancers of interest further refined the evaluable population.

“Excluding individuals with a history of the cancer of interest allowed us to more accurately assess cancer screening,” wrote Chen and co-authors.

Additional results from the study revealed that despite the rebound in monthly cancer screening rates, a deficit in total cancer screenings from January to July 2020 remained compared with January to July 2019. This translated to a United States–population deficit in breast cancer, CRC, and prostate cancer screenings of approximately 3.9 million women, 3.8 million men and women, and 1.6 million men, respectively. Moreover, the total deficit in cancer screenings was estimated at 9.4 million individuals in 2020 compared with 2019.

By geographic region, the Northeastern United States reported the sharpest decline in cancer screenings in March, April, and May for all 3 cancer types. The Western region had a slower recovery in screening during June and July compared with the Midwest and South regions.

Regarding socioeconomic status, prior to the pandemic, screening rates were higher for all 3 cancer types in the highest 2 socioeconomic index quartiles compared with the lower 2 socioeconomic index quartiles. However, the highest socioeconomic index quartile reported the largest decline in screening for all 3 cancer types from January to July 2020 compared with the same period in 2019. Moreover, the decline narrowed the gap in screening rates across the quartiles in 2020 vs 2019.

Other key findings from the study showed that increasing age was associated with less screening in all 3 cancer types. Individuals in the higher quartiles were screened less for breast cancer and CRC in April 2020 compared with individuals in the lower quartiles.

Notably, individuals who utilized telemedicine services had higher rates of cancer screening across the 3 cancer types evaluated.

“Telehealth has a measurable positive effect on whether patients get their cancer screenings,” Chen said.2 “This study also justifies a continued use of telehealth even after the pandemic.”

Chen and co-authors reported that analyzing only insured individuals, the lack of racial/ethnic diversity in the study population, the use of nonspecific codes for screening, and the inclusion of individuals without a history of cancer were limitations of the study.

“As a physician, I wasn’t surprised to see that screenings had declined, but this study measures by how much. There needs to be a concerted public health educational campaign across the country to reinforce the importance of cancer screening. Hospitals across the country also need to devote effort to contact patients to reschedule canceled screening tests, in order to minimize the delay in screening and cancer diagnoses from the missed tests,” concluded Chen.2

Chen RC, Haynes K, Du S, et al. Association of cancer screening deficit in the United States with the COVID-19 pandemic. 

. Published online April 29, 2021. Accessed May 13, 2021. doi:10.1001/jamaoncol.2021.0884

Massive negative impact of COVID-19 on cancer screenings quantified in KU Medical Center faculty study published in JAMA Oncology. News release. April 29, 2021. Accessed May 13, 2021. https://bit.ly/3ojB2fJ.

This article was originally published on OncLive as, "

Routine Screening Rates for Breast, Colorectal, and Prostate Cancers Decline During COVID-19 Pandemic

Public health efforts must address new methods of cancer screening, an expert says.

Routine Cancer Screening Declined During the COVID-19 Pandemic

The FDA has approved piflufolastat F 18 (Pylarify) injection, a prostate-specific membrane antigen (PSMA)–targeted positron emission tomography (PET) imaging agent, to identify suspected metastasis or recurrence of prostate cancer.

The product will be made immediately available to parts of the mid-Atlantic and southern regions, according to Lantheus Holdings, Inc. Moreover, availability is expected to undergo rapid expansion over the next 6 months, with broad availability across the United States expected by the end of the year.

“The FDA approval of [piflufolastat F 18] is a significant milestone for Lantheus and the prostate cancer community in the United States. We believe [piflufolastat F 18] represents a paradigm shift in the identification and management of patients with suspected metastasis or recurrent prostate cancer, providing more accurate and earlier detection of disease than conventional imaging so that doctors, along with patients and their families, can make more informed treatment decisions,” Mary Anne Heino, president and chief executive officer of Lantheus, stated in a press release. “I would like to thank the patients who participated in our clinical trials, the study investigators and our employees, whose efforts made this achievement possible.”

The product was developed to target PSMA, a protein that is overexpressed on the surface of upward of 90% of primary and metastatic prostate cancer cells. The agent adheres to the target, enabling the reader of the PET scan to identify and locate the disease. Cyclotron production of F 18 offers high-batch capacity and high image resolution, and the agent's 110-minute half-life allows for broad geographic distribution.

The regulatory decision was supported by data from 2 pivotal studies: OSPREY and CONDOR; these trials were designed to establish the safety and diagnostic performance of the imaging agent across the prostate cancer disease continuum.

Results from cohort A of the OSPREY study indicated improvement in specificity and positive predictive value (PPV) of the product PET imaging vs conventional imaging in patients at risk for metastatic prostate cancer before initial therapy. In the CONDOR study, investigators enrolled patients with biochemical recurrent prostate cancer. In this patient population and non-informative baseline imaging, the agent was found to have high correct localization and detection rates, including in those with low PSA values, defined as a median PSA 0.8 ng/mL.

In the clinical trials, the product was determined to be well tolerated. In OSPREY and CONDOR, 593 patients with various states of prostate cancer were exposed to a single dose of the agent. Adverse effects such as headache, dysgeusia and fatigue were reported in 2% or less of patients within the studies. Moreover, a delayed hypersensitivity reaction was reported in one patient (0.2%) who had a history of allergic reaction.

Lantheus receives US FDA approval of PYLARIFY (piflufolistat F 18) injection, the first and only commercially available PSMA PET imaging agent for prostate cancer. News release. Lantheus Holdings, Inc. May 27, 2021. Accessed May 27, 2021. https://bwnews.pr/2SynyAS

FDA Approves Piflufolastat F 18 PSMA PET Imaging Agent for Prostate Cancer

The FDA has approved piflufolastat F 18 injection, a prostate-specific membrane antigen–targeted positron emission tomography imaging agent to identify suspected metastasis or recurrence of prostate cancer.

There is an association between increased prostate-specific antigen (PSA) screening and improved outcomes in younger African American patients, according to findings presented in a presscast in advance of the 2021 ASCO Annual Meeting.

In this population, an increase in the frequency of PSA screening was linked to a nearly 25% reduction in prostate cancer–specific mortality and an approximately 40% lower risk of having metastatic disease at the time of a prostate cancer diagnosis.

“We found that PSA screening was associated with a decreased risk of Gleason score ≥8, PSA >20, and metastatic disease at diagnosis, as well as prostate cancer–specific mortality. Taken together, these results would suggest that [increased] PSA screening may improve cancer outcomes for young African American men. Although the results of this study are just one step in addressing all of the other racial disparities that still exist in prostate cancer,” said lead author Edmund M. Qiao, BS, of the University of California San Diego.

Overall, the study included 4726 African American men diagnosed with prostate cancer. The mean patient age was 51.8 years. The mean number of previous PSA screening tests was 1.9. The “high PSA screening” group had received an average of 3 prior screening tests and the “low PSA screening” group had received an average of 0.5 prior screening tests.

Regarding disease severity at diagnosis, all key metrics showed that the high PSA screening group had lower severity. Specifically, the rate of patients with Gleason score ≥8 and PSA >20 at diagnosis was 15.3% versus 10.7% and 16.3% versus 7.2% in the lower versus higher screening groups, respectively. Further, the rate of metastatic disease at diagnosis was 4.2% versus 1.4%, respectively, translating to a 39% risk reduction (odd ratio, 0.61; 95% CI, 0.47-0.81; 

Qiao added, “In our statistical model, controlling for the confounders, we found that PSA screening was associated with about a 25% reduction in prostate cancer–specific mortality [hazard ratio, 0.75; 95% CI, 0.59-0.95; 

 = .02].” The confounding factors controlled for in the statistical model included primary care visit rate, age at diagnosis, year of diagnosis, Charlson comorbidity score, employment, marital status, college education, and income.

Regarding the importance of the research, Qiao said, “African American men have the highest mortality rate for prostate cancer; however, the data for PSA screening includes very few African American men and no young African American men between the ages of 40 and 55. This has led to discordant PSA screening recommendations for these patients and as a result, young African American men are an at-risk group that needs additional research to help guide their clinicians and themselves when deciding when to start PSA screening.”

In 2012, the US Preventive Services Task Force (USPSTF) issued a grade D recommendation against the use of PSA screening in the general US population, regardless of age. The current USPSTF PSA screening policy is slightly changed, with a grade C recommendation for men aged 55 to 69 years, meaning in this population, an individual decision on screening should be made based on a physician-clinician discussion of the potential benefits and risks.

While the USPSTF acknowledges that family history and African American race are two of the most significant risk factors for developing prostate cancer, the panel maintains that there is insufficient evidence to issue individualized screening recommendations in any age group based on those factors.

Commenting on the study during the presscast, ASCO President Lori J. Pierce, MD, FASTRO, FASCO, said, “We know African American men are nearly one-and-a-half times more likely to develop prostate cancer and more than twice as likely to die from prostate cancer as White patients. And despite this, young African American men are poorly represented in PSA studies from which evidence-based guidelines are developed. So, this really limits proper PSA guidance screening guidance for African American patients, especially for those who are younger than 55. And so, because we don't have adequate screening data, there are differences in opinion as to what the guidelines should be. And so, this abstract makes a very strong statement to discuss screening at a younger age in African American men.”

1. Qiao E, Kotha N, Nalawade V, et al. Association of increased intensity of prostate-specific antigen screening in younger African American men with improved prostate cancer outcomes. Presented at: 2021 ASCO Annual Meeting Virtual Embargoed Presscast; May 14, 2021. Abstract 5004.

There is an association between increased prostate-specific antigen (PSA) screening and improved outcomes in younger African American patients.

PSA Screening Leads to Better Outcomes in Young African Americans

The FDA has granted a breakthrough device designation to the Avenda Health Focal Therapy System, a male “lumpectomy” product under development to treat patients with prostate cancer in office while preserving quality of life (QoL), according to an announcement from Avenda Health, the developer of the artificial intelligence (AI)–enabled focal therapy system.

The regulatory designation is only granted to devices that possess the potential to transform the field, providing a new way to treat serious diseases that could be more effective than existing approaches.

The system was designed to spare healthy tissue and minimize toxicity. By using patient-specific data and AI, the device delivers a precise and individualized treatment that only targets the tumor. The treatment can be delivered in a physician’s office with local anesthesia, thus minimizing the downtime of the patient and potentially cutting healthcare costs.

“We are working to advance the treatment of prostate cancer by giving patients and their doctors more options,” Shyam Natarajan, cofounder and chief executive officer of Avenda Health, stated in a press release. “We see our approach as similar to that of a lumpectomy for breast cancer—if the cancerous tumor and appropriate treatment margins can be identified, the standard approach of removing the entire prostate gland and surrounding tissue may not be necessary.”

With the device, physicians are able to precisely ablate tissue and monitor treatment progress in real time.

 They utilize diagnostic data to create an individualized treatment plan. Targeted therapy is then administered through focal laser ablation in the physician’s office with anesthesia. Treatment progress is monitored in real time using sensors to reduce the impact on healthy tissue and preserve QoL.

“Using large datasets of imaging and pathology, Avenda uses AI to calculate precisely where treatment should be applied, sparing healthy tissue so men can maintain urinary and sexual function,” Natarajan stated in a prior release on the device.

 “Diagnosis and treatment can be done in-office by a urologist, rather than multiple specialists and procedures, saving time and costs and offering potentially quick recovery.”

Previously, the FDA granted 510(k) clearance to the device for ablation of soft tissue.

A grant from the National Cancer Institute helped to fund a phase 1 study done in 10 patients, which has recently completed enrollment. Data indicate that the device is safe, with no decline in urinary or sexual function observed in patients over the follow-up period.

Avenda Health granted FDA breakthrough device designation for technology to treat prostate cancer. News release. Avenda Health. May 11, 2021. Accessed May 11, 2021. https://bwnews.pr/2Rbzybl

Focal therapy made easy. Avenda Health. 2020. Accessed May 11, 2021. https://bit.ly/3fgWJcu

Avenda Health uses artificial intelligence to improve prostate cancer treatment. News release. Avenda Health. May 30, 2019. Accessed May 11, 2021. https://bit.ly/3f5djvG

FDA Grants Breakthrough Device Designation to AI-Based Focal Therapy System in Prostate Cancer.

The FDA has granted a breakthrough device designation to the Avenda Health Focal Therapy System, a male “lumpectomy” product under development to treat patients with prostate cancer in office while preserving quality of life.

AI-Based Focal Therapy System Get a Breakthrough Device Designation for Prostate Cancer Treatment

Although the standard-of-care treatment for patients with metastatic pancreatic cancer remains largely unchanged with multi-agent chemotherapy, the role for multidisciplinary care has expanded significantly in recent years, said Andrew E. Hendifar, MD, who added that such an approach to treatment can improve quality of life, alleviate cancer-related complications, and lead to the discovery of relevant genetic predispositions.

“The treatment of [patients with] advanced pancreas cancer, fortunately, is very straightforward. We’ve made some progress; however, when we use multi-agent chemotherapy regimens, some people feel that [we haven’t made] that much progress,” said Hendifar.

“It takes a village to take care of patients with pancreatic cancer; we need medical oncologists, palliative care physicians, dietitians, and genetic counselors involved. That [multidisciplinary] care extends to multiple facets [including] the cancer itself to associated complications, such as diabetes, pain, and weight loss,” Hendifar added.

® during an Institutional Perspectives in Cancer webinar on gastrointestinal malignancies, Hendifar, medical director of Pancreatic Cancer and an assistant professor of medicine at the Samuel Oschin Cancer Center at Cedars-Sinai, discussed considerations for selecting frontline treatment in pancreatic cancer, the growing role of biomarker-driven therapies, and the importance of multidisciplinary care.

®: How are you selecting between the available frontline chemotherapy regimens FOLFIRINOX and gemcitabine plus nab-paclitaxel (Abraxane)?

: The easiest scenario is in the adjuvant setting where FOLFIRINOX has demonstrated superiority to single-agent gemcitabine. In patients who have completed definitive surgery and are medical candidates for FOLFIRINOX, [FOLFIRINOX] would definitely be the way to go. If patients are not medical candidates [for FOLFIRINOX], we have many options.

Choosing between the 2 regimens shouldn’t cause somebody too much grief or consternation because we just don’t have the data to know whether one regimen is superior to the other. When you have a gemcitabine-based or 5-fluorouracil [5-FU]–based first-line regimen, the second-line regimen will be the [alternative].

A lot of times in the clinic, I will discuss the available data and the pros and cons of each regimen with the patient so that we can make the decision together. [I’m] often surprised by how important it is for some patients to not have a port placed or how a continuous infusion is not feasible for some patients based on their social situation.

I try not to get too focused on which regimen we start first. In certain patient subtypes, including the 

-mutant population, we have the same questions about whether we should give gemcitabine plus cisplatin, or FOLFIRINOX.

Fortunately, several clinical trials [are ongoing] to definitively answer that question. One [study] is looking at nanoliposomal irinotecan [nal-IRI], 5-FU and oxaliplatin vs gemcitabine and nab-paclitaxel. The other [study is called] Precision Promise [NCT04229004] and is looking at modified FOLFIRINOX vs gemcitabine plus nab-paclitaxel. Therefore, we have 2 registration clinical trials [ongoing] that will be able to answer that question [of which regimen should be sequenced first].

My guess is that there won’t be much of a long-term survival difference between the 2 [regimens]. We may see a progression-free survival change, but once we switch to a second-line regimen, I can’t imagine it would make a difference.

How could the results of the NAPOLI-3 trial affect the treatment of patients with pancreatic cancer? Do you foresee this regimen being integrated into clinical practice by providers?

NAPOLI-1 firmly places 5-FU plus nal-IRI as the optimal choice for second-line therapy in patients who have received gemcitabine as first-line treatment.

NAPOLI-3 is a registration trial comparing the frontline combination of 5-FU plus nal-IRI and oxaliplatin vs gemcitabine and nab-paclitaxel. This trial is very interesting because it [utilizes] modified oxaliplatin, and the nal-IRI dose has been modified. This is a regimen we would feel very comfortable using in the clinic and is kind of the way we actually manage patients [in this population]. In that sense, it is a very timely trial. It could possibly change the way that we treat patients with pancreatic cancer if [the data] show an improvement with the triplet therapy vs the doublet therapy in terms of survival, as well as tolerability.

What does the future of pancreatic cancer management hold regarding perioperative therapy and biomarker-driven approaches?

As we understand the role of multi-agent first- and second-line treatments, we are also trying to understand the perioperative setting. What is the optimal [perioperative] approach with the current tools available? We are trying to better understand different subgroups of patients and biomarker-related subgroups, such as the DNA damage repair deficient [population], to better understand what we should do.

We are trying to better understand [other populations], such as the 

-mutant groups. Finding those 1 in 100 alterations that are not 

 mutations [is an ongoing challenge, but], that 

 wild-type [population] is a very interesting group of patients to look at.

 mutations go, of course, KRAS inhibitors are on the rise. We have one 

 inhibitor that is [close to being] approved and there are several in development. Unfortunately, 

 G12C is a very rare mutation in pancreatic cancer, but 

 G12D is very common. There are treatments being developed [specifically for 

 G12D mutations]. We are trying to find the right KRAS-directed therapy for these patients.

In the meantime, treatments targeting tumor metabolism is something that should be looked at. We have several in development, including devimistat [CPI-613]. [Pancreas cancer tumors] seem to cause so much weight loss and muscle mass loss, so it makes sense that a treatment targeting tumor metabolism could be the way forward.

Could you elaborate on the rationale to evaluate tumor metabolism–targeting therapies in pancreatic cancer?

 mutations have specific effects on tumor metabolism, specifically regarding the tricarboxylic acid cycle [TCA]. Any therapy that targets TCA cycle metabolism makes a lot of sense to [evaluate] and pancreatic cancer is the perfect test-case for the principle behind this medication. We are very excited about the clinical trial [evaluating this approach] that has completed, and we are eagerly awaiting the results.

Knowing that pancreatic cancer can cause significant complications, such as weight loss, how important is supportive care for these patients?

Therapies for pancreatic cancer are typically intense, multi-agent chemotherapies. They can cause problems such as weight loss, fatigue, and deconditioning, which are inherent in that patient population already. It’s essential that we jump on [supportive care measures, including getting dietitians involved, supplementing pancreatic enzymes, managing pain in effective ways, and using anti-inflammatory agents.

From our understanding, anti-inflammatory agents play a big role in cancer-associated inflammation and cachexia. Also, getting physical therapy involved to get our patients less deconditioned if possible is difficult, but we have to do that in order for patients to be able to receive systemic therapy.

With that in mind, why is integrating a multidisciplinary approach to patient care important in pancreatic cancer?

When we are treating patients with pancreatic cancer, that is the time to rally the troops as much as possible. We want to get everyone involved because this patient group needs help and support [from a multidisciplinary team. Beyond] the medical oncologist, nurses can help explain to patients how to handle their treatments, dietitians can help them with weight loss, and palliative care doctors can help with pain. It may also be appropriate to get genetic counselors involved to make sure patients do not have any predispositions.

It seems like a lot of work, and it is. However, it is what we need to do right now for this patient group until therapies [improve]. One day in the future, I know we are going to say, “Wow, pancreatic cancer is easy [to treat]; we just give this medication, and everything is going to get better.” However, until that happens, the morbidity associated with this disease is immense, so we really need to rally the troops to get everybody together and help our patients.

Multidisciplinary Care Is Paramount as New Therapies Emerge in Metastatic Pancreatic Cancer.

Multidisciplinary care is key to improve quality of life, lessen cancer-related complications, and improve outcomes for patients with pancreatic cancer.

Team-Based Approach Is Key Moving Forward in Pancreatic Cancer Care

Two studies conducted at NYU Grossman School of Medicine and NYU Langone’s Perlmutter Cancer Center found that misinformatoin and bias is prevalent in YouTube videos about prostate and bladder cancer. 

A massive amount of misinformation and bias is being spread in YouTube videos on bladder and prostate cancer, according to 2 studies conducted at NYU Grossman School of Medicine and NYU Langone’s Perlmutter Cancer Center.1

Investigators on the bladder cancer study,2 led by Stacy Loeb, MD, MSc, ranked the overall quality of over two-thirds of the YouTube videos they assessed as poor to moderate. A moderate to high amount of misinformation was noted in 21% of the videos and a commercial bias was found in 17% of the videos.

In the prostate cancer study,3 also led by Loeb, it was discovered that over three-fourths of the videos included content that was potentially misinformative in the video itself or in the comments section. Further, while treatment benefits were highlighted in 75% of the videos, the risks of the treatments were only adequately described in 50%.

For the bladder cancer study, the investigators used these 2 validated instruments to score the quality of the videos: the Patient Education Materials Assessment Tool (PEMAT) and the DISCERN quality criteria for consumer health information.

The researchers found that there were 242,000 bladder cancer videos on YouTube and then used the 2 instruments to evaluate the first 150 of these. Overall, 67% of the 150 videos ranked as poor to moderate using DISCERN. Of concern, over 1 million (1,289,314) viewers watched the 21% of videos that were noted to have a moderate to high amount of misinformation, and 324,287 viewers watched the 17% of videos found by Loeb et al to contain commercial bias.

“Bladder cancer is the second most common urologic cancer worldwide, but evidence is lacking on the accuracy of information available on YouTube, the most popular social network,” Loeb, professor of Urology and Population Health at NYU Grossman School of Medicine and NYU Langone’s Perlmutter Cancer Center, stated in a press release.

“Our findings highlight an urgent need for more accurate, patient-friendly social media content,” added Loeb, who is also the incoming chair of the American Urological Association Public Media Committee.

Loeb et al used the same instruments—DISCERN and PEMAT—for the prostate cancer study that were used in the bladder cancer assessment. The investigators found that there were more than 600,000 videos about prostate cancer on YouTube and assessed the first 150 of these for their study.

Overall, 77% (n = 115) of the videos contained content that was potentially misinformative in the video itself or in the comments section. According to Loeb et al, these 115 videos reached more than 6 million viewers.

The potential benefits of treatments were highlighted in 75% of the 150 videos, while only 53% explained potential side effects and other risks. Further, only half of the videos advocated shared decision-making despite it being a key recommendation in current guidelines. Loeb et al’s analysis also determined that there was a significant negative correlation between the scientific quality of the videos and viewer engagement.

Summarizing her advice to providers on these findings, Loeb said, “Having lots of ‘likes’ and views does not mean that a video is medically accurate. As health-care providers, we can help counter this trend by better communicating with patients and guiding them to trustworthy sources for additional information.”

In the press release highlighting the findings of the studies, Loeb provider several tips for providers:

“Engage in shared decision-making, clearly outlining the benefits and risks of treatment and offering actionable steps for patients.

Encourage patients to learn how to spot medical misinformation.

Arm patients with trustworthy sources of information, such as the Bladder Cancer Advocacy Network, Prostate Cancer Foundation, the Urology Care Foundation, and the National Cancer Institute.

Actively participate in social media to disseminate accurate, evidence-based content.”

1. Many Popular YouTube Videos Spread Misinformation on Bladder & Prostate Cancer, Studies Find. Published online April 27, 2021. Accessed May 5, 2021. https://bit.ly/3xNYXID.

2. Loeb S, Reines K, Abu-Salha Y, et al. Quality of bladder cancer information on YouTube. 

. 2021;79(1):56-59. doi: 10.1016/j.eururo.2020.09.014

3. Loeb S, Sengupta S, Butaney M, et al. Dissemination of misinformative and biased information about prostate cancer on YouTube. 

. 2019;75(4):564-567. doi: 10.1016/j.eururo.2018.10.056

This article was originally published on Urology Times as, "

Studies spotlight misinformation in YouTube bladder and prostate cancer videos

Studies found that misinformation and bias is prevalent in YouTube videos about prostate and bladder cancer. 

YouTube Videos Spread Cancer Misinformation

The novel oral TKI masitinib in combination with docetaxel and prednisone resulted in improved progression-free survival compared with docetaxel plus prednisone in patients with metastatic castration-resistant prostate cancer (CRPC), meeting the predefined primary end point of the phase 2b/3 AB12003 trial (NCT03761225).1

Patents associated with the data from the study are being filed. Once submitted, detailed findings will be shared during a webcast with key opinion leaders, according to the pharmaceutical company AB Science.

Masitinib was developed to target mast cells and macrophages, which are both key players in cell immunity; the drug does this by hindering a small number of kinases. The mechanism of action of the TKI allows for its use in many conditions within the field of oncology, in inflammatory diseases, and in select central nervous system (CNS) diseases.

Because masitinib has an immunotherapy effect, the agent is hypothesized to favorably impact survival when used either alone or in combination with chemotherapy in patients with cancer. Masitinib has showcased activity on mast cells and microglia, which inhibits the activation of the inflammatory process. As such, the drug is able to impact symptoms experienced with select inflammatory and CNS diseases and the deterioration of such diseases.

In the international, multicenter, randomized, double-blind, placebo-controlled, 2-parallel group, phase 3 trial, investigators enrolled chemotherapy-eligible patients with metastatic CRPC.

To be eligible for enrollment, patients had to have histologically or cytologically confirmed metastatic CRPC that was either pretreated with abiraterone acetate (Zytiga) and had documented disease progression or indicated for the initiation of docetaxel treatment.2 Patients also had to have evidence of progressive metastatic disease per Prostate Cancer Clinical Trials Working Group 2 recommendations and have acceptable organ function per the study protocol. If patients had previously received chemotherapy, they were excluded.

Those in the investigative arm received masitinib at a dose of 6.0 mg/kg/day twice daily, in combination with docetaxel at 75 mg/m2 once every 3 weeks for 6 cycles, plus prednisone per standard clinical practice. Patients in the control arm were given placebo plus docetaxel and prednisone at the same dosing and schedule.

The primary end point of the trial is PFS, while overall survival (OS) serves as a secondary end point.

Patient enrollment to the trial was given the green light by the FDA in January 2020, after the company’s investigational new drug application was cleared for the agent’s use in patients with metastatic CRPC who were eligible for chemotherapy.3

In June 2018, an interim analysis was conducted by an independent data monitoring committee. Based on the rules for the assessment, the committee recommended to continue the study in a prespecified subgroup of patients who had been identified by a biomarker.

The probability of success of the trial was projected to exceed 80% in this subgroup per the statistical rule of the protocol at the time of the analysis, with the assumption that patients yet to be enrolled at the time would behave like those who had been analyzed. The subgroup was expected to account for about two-thirds of the population.

Previously, the agent was evaluated in a phase 1/2 trial, which evaluated its use in combination with docetaxel in patients with hormone refractory prostate cancer who experienced disease progression following first-line treatment.4

The novel oral TKI masitinib in combination with docetaxel and prednisone resulted in improved progression-free survival compared with docetaxel plus prednisone in patients with metastatic castration-resistant prostate cancer, meeting the predefined primary end point of the phase 2b/3 AB12003 trial.

Genitourinary Cancer