Jason Broderick

Data from a recent study demonstrated that increased prostate-specific antigen (PSA) screening was associated with improved outcomes in younger Black patients with prostate cancer.

Among this patient population, an increased 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 … 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,” said lead study author Edmund M. Qiao, of the University of California San Diego, during a presentation of the data on a news briefing held ahead of the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting.

A blood test and PSA screening may indicate the presence of prostate cancer. However, other conditions, such as an inflamed prostate, can increase PSA levels, which is why there is conflicting advice involving screening.

Overall, the study included 4,726 Black men (mean age, 51.8 years) diagnosed with prostate cancer. The “high PSA screening” group had received an average of three 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 important metrics showed that the high PSA screening group had lower severity. The rate of metastatic disease at diagnosis was 4.2% versus 1.4%, respectively, translating to a 39% risk reduction.

“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,” noted Qiao. The confounding factors controlled for in the statistical model included primary care visit rate, age at diagnosis, year of diagnosis, employment, marital status, college education and income.

Black men have the highest mortality rate in prostate cancer, Qiao noted. Prior to this research, he highlighted, there has been limited data on PSA screening in this patient population.

“The data for PSA screening includes very few African American men (in general) and no young African American men between the ages of 40 and 55,” he said. “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 U.S. Preventive Services Task Force (USPSTF) issued a grade D recommendation against the use of PSA screening in the general U.S. 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 Black 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.

“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,” ASCO President Dr. Lori J. Pierce said during the news briefing. “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.”

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The study results lend strength to discuss prostate cancer screening in younger Black men, according to an expert.

Increased Screening Associated with Improved Outcomes in Younger Black Patients with Prostate Cancer

Sprycel (dasatinib), an oral medication that helps reduce the production of damaged white blood cells in the body, has been approved by the Food and Drug Administration (FDA) for the treatment of pediatric patients with Philadelphia chromosome-positive (Ph+) chronic myeloid leukemia (CML) in chronic phase (CP).

The approval is based on results with Sprycel demonstrated in 97 pediatric patients with CP-CML enrolled across two studies, an open-label, nonrandomized, single-arm phase 2 trial and an open-label, nonrandomized, dose-ranging phase 1 trial. Fifty-one patients (all from the single-arm trial) were newly diagnosed, and the remaining 46 (29 from the single-arm study and 17 from the dose-ranging trial) were intolerant or resistant to prior Gleevec (imatinib).

At a median follow-up of 4.5 years, more than half of the responding patients in the treatment-naïve cohort had not progressed at the time of the data cutoff, so the median duration of complete cytogenetic response (CCyR), major cytogenetic response (MCyR), and major molecular response (MMR) could not be estimated. The same was true at the median follow-up time of 5.2 years for the previously treated cohort.

The range of duration of response (DOR) for the newly diagnosed patients was 2.5+ to 66.5+ months for CCyR, 1.4 to 66.5+ months for MCyR, 5.4+ to 72.5+ months for patients who achieved MMR by month 24, and 0.03+ to 72.5+ months for patients who achieved MMR at any time. The ‘+’ denotes a censored observation. Among the Gleevec-intolerant cohort, the DOR ranges were 2.4 to 86.9+ months for CCyR, 2.4 to 86.9+ months for MCyR, and 2.6+ to 73.6+ months for MMR.

“Options for pediatric patients with chronic myeloid leukemia are limited, and it is challenging to conduct clinical trials investigating potential new treatments in this small patient population,” Lia Gore, M.D., University of Colorado School of Medicine and Children’s Hospital Colorado, said in a statement. “Dasatinib is an important new option to help address the unmet needs of children with Philadelphia chromosome-positive CML in chronic phase.”

The 3-, 6-, 12- and 24-month CCyR rates among newly diagnosed patients were 43.1 percent, 66.7 percent, 96.1 percent and 96.1 percent, respectively. In the previously treated group, the corresponding rates were 45.7 percent, 71.7 percent, 78.3 percent and 82.6 percent, respectively.

The 3-, 6-, 12- and 24-month MCyR rates among treatment-naive patients were 60.8 percent, 90.2 percent, 98.0 percent and 98.0 percent, respectively. The corresponding rates in the Gleevec-intolerant group were 60.9 percent, 82.6 percent, 89.1 percent and 89.1 percent, respectively.

The 3-, 6-, 12- and 24-month MMR rates among newly diagnosed patients were 7.8 percent, 31.4 percent, 56.9 percent and 74.5 percent, respectively. The corresponding rates in the previously treated group were 15.2 percent, 26.1 percent, 39.1 percent and 52.2 percent, respectively.

Across both patient groups, 14.4 percent experienced treatment-related serious adverse events (AEs). AEs occurring in 15 percent or more of patients included myelosuppression, headache, nausea, diarrhea, skin rash, pain in extremity and abdominal pain.

“While chronic myeloid leukemia is rare in children, accounting for less than three percent of all pediatric leukemias, it is often more aggressive in younger patients than in adults and until recently, there have been few available treatment options,” Vickie Buenger, President, Coalition Against Childhood Cancer, said in a statement. “The FDA’s decision to approve the expanded use of Sprycel in children with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase may bring new hope to these patients and their families.”

Sprycel (dasatinib), an oral medication that helps reduce the production of damaged white blood cells, has been approved by the Food and Drug Administration for the treatment of pediatric patients with Philadelphia chromosome-positive chronic myeloid leukemia in chronic phase.
 

Sprycel Approved for CML Subset

The FDA has granted an accelerated approval to Tecentriq (atezolizumab) as a frontline treatment for patients with locally advanced or metastatic urothelial carcinoma (mUC) who are not eligible for cisplatin chemotherapy. The approval was announced by Genentech, the immunotherapy drug’s manufacturer.

“It is encouraging to see continued progress in the treatment of advanced bladder cancer, which until last year had not seen any major advancements in more than 30 years,” said Andrea Maddox Smith, chief executive officer, Bladder Cancer Advocacy Network. “We are excited that Tecentriq is now a treatment option for people with advanced bladder cancer who are unable to receive a cisplatin-based chemotherapy as an initial treatment.”

The approval is based on data from the single-arm phase II IMvigor210 trial. In a study cohort of 119 cisplatin-ineligible, treatment-naive patients, the objective response rate with Tecentriq was 23.5 percent, including a complete response rate of 6.7 percent.

Tecentriq was previously approved for people with locally advanced or mUC who have disease progression during or following any platinum-containing chemotherapy, or within 12 months of receiving chemotherapy before surgery or after surgery.

“We are pleased that Tecentriq will now be available to more people with advanced bladder cancer, including those who are unable to receive initial treatment with cisplatin chemotherapy,” said Sandra Horning, MD, chief medical officer and head of Global Product Development at Genentech.

“Tecentriq was the first cancer immunotherapy approved by the FDA for people with advanced bladder cancer and has become a standard of care in those whose disease has progressed after receiving other medicines, either before or after surgery, or after their disease has spread.”

The IMvigor210 cohort enrolled 123 patients with cisplatin-ineligible locally advanced or mUC at 47 locations in North America and Europe between June 9, 2014, and March 30, 2015. Patients received 1200 mg of intravenous Tecentriq every three weeks until progression. The primary endpoint was objective response rate, with secondary outcomes measures including progression-free survival and overall survival.

Among the 123 patients, 119 received at least one dose of Tecentriq. Responses occurred regardless of PD-L1 status and across poor prognostic factor subgroups. The median duration of response was not reached. There was an association between tumor mutation load and response. The median progression-free survival was 2.7 months and overall survival was 15.9 months.

The most common grade 3/4 adverse events included fatigue (8 percent), urinary tract infection (5 percent), anemia (7 percent), diarrhea (5 percent), increase in the level of creatinine in the blood (5percent), increase of the liver enzyme alanine transaminase (4 percent), hyponatremia (15percent), decreased appetite (3 percent), and back/neck pain (3 percent).

Adverse events led to 5 patients discontinuing treatment. Five patients died, due to sepsis, cardiac arrest, myocardial infarction, respiratory failure, and respiratory distress. An additional patient had inflammation of the brain due to the herpes simplex virus and disease progression at the time of death.

The accelerated approvals of Tecentriq are contingent on results from an ongoing confirmatory phase III study, IMvigor 211 (NCT02302807), which is comparing Tecentriq with chemotherapy in patients with locally advanced or metastatic urothelial bladder cancer in the frontline setting and after progression on at least one prior platinum-containing regimen.

The FDA has granted an accelerated approval to Tecentriq as a frontline treatment for patients with locally advanced or metastatic urothelial carcinoma who are not eligible for cisplatin chemotherapy.

Tecentriq Approved as First-Line Treatment for Some Patients With Bladder Cancer

The PALOMA-3 trial examining an Ibrance (palbociclib) regimen in HR-positive/HER2-negative breast cancer was halted after an independent panel determined it met the primary endpoint of improving progression-free survival (PFS). The results were announced by Pfizer, the company developing Ibrance, which noted that these are the first randomized phase 3 data reported for the CDK 4/6 inhibitor.

“We’re gratified to be able to stop the trial early and are engaging in discussions with health authorities regarding a regulatory path forward,” Mace Rothenberg, senior vice president of Clinical Development and Medical Affairs and chief medical officer for Pfizer Oncology, said in a statement.

The multicenter PALOMA-3 study randomized 521 patients with metastatic breast cancer whose disease progressed on or following endocrine treatment in a 2:1 ratio to fulvestrant plus either placebo or Ibrance. Faslodex was administered at 500 mg (IM) on days 1 and 15 of cycle 1, and then on day 1 of each cycle thereafter, and patients received oral Ibrance at 125 mg/day continuously for the first 3 weeks of each cycle, followed by 1 week off. Treatment cycles were 28 days for both arms.

Beyond the primary PFS endpoint, secondary endpoints for the trial included overall survival, objective response, and duration of response. The adverse events reported for the Ibrance/fulvestrant combination were commensurate with those observed with previous single-agent use of the drugs. Pfizer intends to submit the full results from the study for presentation at the 2015 American Society of Clinical Oncology (ASCO) Annual Meeting in June.

While not approved for the use explored in PALOMA-3, Ibrance has received an accelerated approval as a frontline treatment for postmenopausal women with ER-positive, HER2-negative metastatic breast cancer, based on findings from the phase 2 PALOMA-1 trial.

In the open-label phase 2 study, treatment with Ibrance plus letrozole reduced the risk of disease progression by 51 percent compared with letrozole alone. The median PFS with Ibrance was 20.2 versus 10.2 months for letrozole alone.

PALOMA-1 trial randomized 165 postmenopausal patients with ER-positive, HER2-negative advanced breast cancer in a 1:1 ratio in two parts: Part 1 contained 66 patients and Part 2 had 99 patients. Continuous daily letrozole was administered at 2.5 mg with or without Ibrance at 125 mg daily for 3 weeks followed by 1 week of rest until progression. The primary endpoint was PFS by investigator assessment.

The rate of grade 3/4 neutropenia was significantly higher in the Ibrance arm compared with letrozole alone (54 percent versus 1 percent). Additionally, the rate of grade 3/4 leucopenia (19 percent versus 0 percent) and fatigue (4 percent versus 1 percent) were higher with Ibrance. No cases of febrile neutropenia or neutropenia-related infections were reported in the study.

Altogether, 13 percent of patients discontinued treatment as a result of side effects in the Ibrance arm compared with 2 percent for letrozole. The most frequently reported serious adverse events with the combination were pulmonary embolism (4 percent) and diarrhea (2 percent).

At the time of approval, PALOMA-1 coauthor Dennis Slamon heralded the decision. “With the FDA approval, this study represents a potential practice-changing result. I believe palbociclib will now become a standard treatment approach for postmenopausal women with ER+/HER2- metastatic breast cancer,” Slamon, a professor of medicine and director of the Revlon/UCLA Women’s Cancer Research Program, said in a statement.

The confirmatory phase 3 trial for Ibrance's accelerated approval is PALOMA-2. This study is comparing the combination of Ibrance and letrozole with letrozole alone as a frontline treatment for postmenopausal women with ER-positive, HER2-negative advanced breast cancer (NCT01740427).

As Pfizer awaits the PALOMA-2 data, Rothenberg noted that the company is pleased with what the PALOMA-3 outcomes have shown. “The results of this trial are especially important because they help us understand the potential of Ibrance to improve outcomes in patients with this difficult to treat cancer.”

The PALOMA-3 trial examining an Ibrance (palbociclib) regimen in HR-positive/HER2-negative breast cancer was halted after an independent panel determined it met the primary endpoint of improving progression-free survival.

Jason Broderick

Increased Screening Associated with Improved Outcomes in Younger Black Patients with Prostate Cancer

Sprycel Approved for CML Subset

Tecentriq Approved as First-Line Treatment for Some Patients With Bladder Cancer

Ibrance Delays Progression of Breast Cancer in Phase 3 Trial

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