FDA granted regular approval to venetoclax

 (Venclexta) in combination with azacitidine (Vidaza), decitabine, or low dose cytarabine (LDAC) for adults 75 years or older with newly diagnosed acute myeloid leukemia (AML) or those who have comorbidities precluding intensive induction chemotherapy.

The FDA initially granted accelerated approval to venetoclax for this indication in November 2018. The efficacy of venetoclax was therefore confirmed in 2 randomized, double-blind, placebo-controlled trials in the aforementioned patient population, including in the VIALE-A (NCT02993523) study and the VIALE-C study (NCT03069352).

This review was conducted under Project Orbis, where the FDA collaborated with the Australian Therapeutic Goods Administration, the Brazilian Health Regulatory Agency, Health Canada, and Switzerland’s Swissmedic.

Further, using the real-time oncology review (RTOR) pilot program, and the assessment aid, the application for the venetoclax combination was approved 5 weeks ahead of the FDA PDUFA date.

In an interview with CancerNetwork®, Courtney DiNardo, MD, MSCE, associate professor in the department of Leukemia at The University of Texas MD Anderson Cancer Center in Houston, discussed this recent approval and what it means for patients with AML.

This segment comes from the CancerNetwork® portion of the MJH Life Sciences Medical World News, airing daily on all MJH Life Sciences channels.

FDA grants regular approval to venetoclax in combination for untreated acute myeloid leukemia [news release]. FDA. Published October 16, 2020. Accessed October 29, 2020. https://www.fda.gov/drugs/drug-approvals-and-databases/fda-grants-regular-approval-venetoclax-combination-untreated-acute-myeloid-leukemia

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Venetoclax was granted approval in combination with azacitidine, decitabine, or low dose cytarabine earlier this month for adults 75 years or older with newly diagnosed acute myeloid leukemia or those who have comorbidities precluding intensive induction chemotherapy.

Courtney D. DiNardo, MD, MSCE, on the Approval of a Venetoclax Combo in Older Adults with AML

New clinical guidelines from the American Society for Radiation Oncology (ASTRO) published in 

 provided guidance for physicians who use radiation therapy to treat patients with locally advanced rectal cancer.

The updated guidelines, which replace ASTRO’s 2016 guidance for rectal cancer, outlined indications and best practices for pelvic radiation treatments, as well as the integration of radiation with chemotherapy and surgery for patients with stage II to III disease.

“As rectal cancer becomes more of a disease of younger adults, long-term survivorship and quality of life considerations become even more important,” Prajnan Das, MD, MPH, chair of the rectal guideline task force, as well as professor and chief of gastrointestinal radiation oncology at The University of Texas MD Anderson Cancer Center in Houston, said in a press release.

 “Part of our motivation was to create guidelines that provide options for different treatments that could potentially improve survival rates and also help preserve patients' quality of life.”

More specifically, the recommendations in the guideline address patient selection for radiation therapy, delivery of pelvic radiation treatments, options for non-operative management of locally advanced rectal cancer, and guidance for follow-up care. Key recommendations with the updated guidelines include:

For patients with clinical stage II-III rectal cancer, neoadjuvant radiation therapy is strongly recommended to reduce their risk of locoregional recurrence. Moreover, the guidelines suggest that radiation therapy for locally advanced rectal cancer should be performed before rather than after surgery. Radiation may also be omitted in favor of upfront surgery for some patients at low risk of recurrence, after discussion with a multidisciplinary care team. Nonetheless, clinical staging involving a physical exam and pelvic MRI is crucial in determining which patients should receive neoadjuvant radiation therapy.

Both conventionally fractionated radiation and short-course radiation are recommended equally for patients who require neoadjuvant radiation therapy, given that researchers have observed high-quality evidence for similar efficacy and patient-reported quality of life outcomes with each treatment. The guidelines also specifically outline optimal dosing, fractionation, and delivery techniques for radiation therapy.

The updated recommendations also addressed how to incorporate chemotherapy into the pre-operative setting for patients who are at high risk of recurrence and who would likely benefit from additional treatment using a total neoadjuvant therapy (TNT) approach. Further, the guidelines highlighted other sequencing and timing issues for radiation, chemotherapy and surgery, with specific attention given to treatment tolerability and potential downstaging.

Organ preservation approaches (i.e., non-operative management and local excision) may present an alternative to radical surgery for select patients according to the ASTRO recommendations, especially those who would have a permanent colostomy or inadequate bowel continence after surgery. Notably, the guideline lays out distinguishing criteria for situations where surgery can be avoided, as well as long-term surveillance and care for such patients.

“Different treatments are appropriate for different patients, and the oncology field at large is moving toward personalized care,” Jennifer Y. Wo, MD, vice chair of the rectal guideline task force and associate professor of radiation oncology at Harvard Medical School and Massachusetts General Hospital in Boston, said in the release. “Some patients may need less than what is considered a typical course of treatment, while some patients may need more. This guideline focuses on providing options that can be tailored to patients' characteristics and their wishes.”

Importantly, though the updated guidelines were completed before the coronavirus disease 2019 (COVID-19) pandemic, the recommendations outlined by ASTRO can still guide clinics as they continue to care for patients. Furthermore, to reduce how frequently patients needed to come into the clinic for treatment, many institutions moved toward short-course radiation in the early months of the pandemic, which aligns with the guideline's recommendations.

“We have yet to see the true impact of COVID-19, but we know that interruptions in screening likely will lead to fewer patients receiving treatment when their disease is more manageable,” Wo added. “And if that does happen and we start seeing patients with more advanced disease, then the parts of the guidelines that specifically address treatment for high-risk patients will become even more important."

1. Wo JY, Anker CJ, Ashman JB, et al. Radiation Therapy for Rectal Cancer: Executive Summary of an ASTRO Clinical Practice Guideline. 

2. ASTRO issues clinical guideline on radiation therapy for rectal cancer [news release]. Arlington, Virginia. Published October 21, 2020. Accessed October 29, 2020. https://www.newswise.com/articles/astro-issues-clinical-guideline-on-radiation-therapy-for-rectal-cancer?sc=sphr&xy=10021790

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The updated guidelines outlined indications and best practices for pelvic radiation treatments, as well as the integration of radiation with chemotherapy and surgery for patients with stage II to III disease.

ASTRO Releases New Clinical Guidelines for Use of Radiation Therapy in Locally Advanced Rectal Cancer

 indicated that the impact of coronavirus disease 2019 (COVID-19) on cancer care in the US has led to decreases and delays in identifying new cancers, as well as the delivery of treatment.

Moving forward, researchers suggested that if these problems remain unresolved, there will be an increase in cancer morbidity and mortality for years to come.

“If cancers are not diagnosed at an early stage, we could face rising death rates for several years to come,” co-author Michael Diaz, MD, assistant managing physician at the Florida Cancer Specialists & Research Institute (FCS) and president of the Community Oncology Alliance (COA), said in a press release.

 “It is critical that adults with a family history of cancer and others who may be experiencing symptoms do not delay their screenings for the fear of being exposed to or contracting coronavirus. Medical practices now have numerous strategies in place to protect the safety and health of patients, doctors, nurses and other staff members.”

For this study, the investigators utilized a large medical claims clearinghouse database representing 5% to 7% of the Medicare Fee for Service (FFS) population in order to characterize changes in the use of cancer care services and to gain insight into the impact of COVID-19 on the patients with cancer in the US, including identification of new patients, gaps in access to care, and disruption of treatment journeys. Overall, 6,227,474 Medicare FFS claims were captured by the analysis.

Compared to the baseline period of March to July 2019, in March to July 2020 there was a substantial decrease in cancer screening, visits, therapy, and surgeries, though this varied by cancer type and site of service. Specifically, at the peak of the pandemic in April, screening for breast, colon, prostate, and lung cancer were all lower by 85%, 75%, 74%, and 56%, respectively.

Moreover, researchers also observed significant utilization reductions in April for hospital outpatient Evaluation and Management (E&M) visits (-74%), new patient E&M visits (-70%), and established patient E&M visits (-60%). Additionally, a decrease in billing frequency was revealed for the top physician-administered oncology products, declining in both April (-26%) and July (-31%). Further, mastectomies were also steadily reduced from April through July, with colectomies comparably reduced in April and May and prostatectomies dipping in April and July.

“In the early months of the pandemic, many people chose or had to delay or even skip regular screenings, such as mammograms, prostate exam, PSA testing or colonoscopies, among others, for various types of cancer,” explained co-author Lucio Gordan, MD, president and managing physician at FCS, in the release. “This has resulted in later diagnoses for some patients and delays in beginning treatment. Oncologists are preparing their practices for significant impact in cancer patient outcomes due to these delays.”

However, one positive impact of COVID-19 revealed by the study was the rapid adoption of telehealth and other strategies by various community oncology practices.

“Community oncologists and their team members showed incredible resilience and resolve to deal with this severe crisis, by adopting telehealth very quickly, reorganizing workflows, enhancing safety processes at their clinics, and migrating staff to work from home, among other strategies,” Gordan added. “Although a decrease in services was inevitable, the resolve of these practitioners and staff handled and avoided what could have been a much worse situation.”

In order to effectively diagnose and manage cancer moving forward, the investigators recommended that stakeholders consider how to heighten awareness of the dangers of medical distancing and recover patients’, especially senior patients’, confidence in their ability to seek safe and appropriate care, including routine cancer screening and appropriate cancer treatment. According to the researchers, policies which promote access to cancer care and support the cancer ecosystem also have the potential to reduce the expected morbidity and mortality in this patient population.

Nevertheless, future studies remain necessary to help understand the impact of COVID-19 on specific patient populations.

1. Pratt D, Gordan L, Diaz M, et al. The Impact of COVID-19 on Cancer Care: How the pandemic is delaying cancer diagnosis and treatment for American seniors. 

2. New Study Warns of Negative Impact COVID-19 is Having on Cancer Screenings, Diagnosis and Treatment [news release]. Fort Myers, Florida. Published October 28, 2020. Accessed October 29, 2020. https://flcancer.com/en/articles/new-study-warns-negative-impact-covid-19-having-cancer-screenings-diagnosis-and-treatment/

This study found that the impact of COVID-19 on cancer care in the US has led to decreases and delays in identifying new cancers, as well as the delivery of treatment.

Impact of COVID-19 on Cancer Care May Lead to Increase in Cancer Morbidity and Mortality

The FDA has approved expanded claims for the Cobas EGFR Mutation Test v2 as a companion diagnostic for a broader group of therapies in the treatment of non-small cell lung cancer (NSCLC), according to Roche, the developer of the companion diagnostic.

The cobas EGFR Mutation Test v2 is a real-time polymerase chain reaction test for the qualitative detection of defined mutations of the 

 gene in patients with NSCLC, with results typically available in less than 8 hours.

The expansion now allows the test to be used as a companion diagnostic for all 5 FDA-approved EGFR tyrosine kinase inhibitor (TKI) therapies targeting 

 mutations L858R and Exon 19 Deletions in accordance with the approved therapeutic product labelling. Additionally, the group claim will also allow the test to be used as a companion diagnostic for any EGFR TKI therapies targeting the same mutations approved in the future, without the need to conduct individual clinical studies with the test for each new therapy.

Importantly, this is the first companion diagnostic approved for this group of therapies in patients with NSCLC.

“Clinicians can now have greater confidence in the robustness, reliability and proven clinical utility of the cobas EGFR Mutation Test v2 when evaluating lung cancer patients who may benefit from targeted EGFR TKI therapies,” Neil Gunn, head of Roche Sequencing Solutions, said in a press release. “By approving a single test for a broad group of therapies, this new and innovative approach by the FDA can pave the way for future EGFR TKI therapies to utilize the cobas EGFR Mutation Test v2 to help identify patients for personalized medicine.”

Roche receives FDA approval for the cobas EGFR Mutation Test v2 as the first companion diagnostic test for expanded EGFR TKI therapies in patients with non-small cell lung cancer [news release]. Pleasanton, California. Published October 29, 2020. Accessed October 30, 2020. https://www.prnewswire.com/news-releases/roche-receives-fda-approval-for-the-cobas-egfr-mutation-test-v2-as-the-first-companion-diagnostic-test-for-expanded-egfr-tki-therapies-in-patients-with-non-small-cell-lung-cancer-301163170.html

The FDA approved expanded claims for the cobas EGFR Mutation Test v2 as a companion diagnostic for a broader group of therapies in the treatment of non-small cell lung cancer.

FDA Approves First Companion Diagnostic for Expanded EGFR TKI Therapies in NSCLC

Patients who participated in the Beat AML Master clinical trial were found to have superior outcomes with precision medicine, compared to patients with acute myeloid leukemia (AML) who opted for standard chemotherapy treatment, according to a study published in 

Overall, the study demonstrated that a precision medicine therapy strategy in AML is feasible within 7 days of sample receipt and before treatment selection, allowing patients and physicians to rapidly incorporate genomic data into treatment decisions without increasing early death or adversely impacting overall survival (OS).

“The study shows that delaying treatment up to seven days is feasible and safe, and that patients who opted for the precision medicine approach experienced a lower early death rate and superior overall survival compared to patients who opted for standard of care,” corresponding author John C. Byrd, MD, D. Warren Brown Chair of Leukemia Research of The Ohio State University, said in a press release.

 “This patient-centric study shows that we can move away from chemotherapy treatment for patients who won’t respond or can’t withstand the harsh effects of the same chemotherapies we’ve been using for 40 years and match them with a treatment better suited for their individual case.”

In the ongoing Beat AML trial, researchers prospectively enrolled untreated patients with AML who were 60 years or older with the aims of providing cytogenetic and mutational data within 7 days of the sample receipt and before treatment selection, followed by treatment assignment to a sub-study based on the dominant clone. In total, 487 patients with suspected AML were enrolled in the study and 395 were deemed eligible for analysis.

The median age of the participants was 72 years (range 60-92 years). Overall, 374 patients (94.7%) had genetic and cytogenetic analysis completed within 7 days and were centrally assigned to a Beat AML sub-study, while 224 (56.7%) were enrolled on a Beat AML sub-study. The remaining 171 patients elected to receive either standard of care (n = 103), investigational therapy (n = 28), or palliative care (n = 40). Moreover, 9 patients died before treatment assignment.

Demographic, laboratory, and molecular characteristics were not found to be significantly different between patients on the Beat AML sub-studies and those receiving standard of care (induction with cytarabine + daunorubicin [7 + 3 or equivalent] or hypomethylation agent).

However, 30-day mortality was less frequent, and OS was significantly longer for patients enrolled on the Beat AML sub-studies versus those who elected to receive standard of care. The median OS for patients included in the Beat AML trial was 12.8 months versus 3.9 months for patients opting for standard of care.

To date, the trial has now screened more than 1000 patients at 16 cancer centers. The data presented herein represents patient enrollment during a slice of time between November 17, 2016 and January 30, 2018.

“The study is changing significantly the way we look at treating patients with AML, showing that precision medicine, giving the right treatment to the right patient at the right time, can improve short and long-term outcomes for patients with this deadly blood cancer,” Louis J. DeGennaro, PhD, president and CEO of the Leukemia & Lymphoma Society (LLS), the conductor of the trial, said in the release. “Further, Beat AML has proven to be a viable model for other cancer clinical trials to emulate.”

Recently, LLS launched its Beat COVID trial, which leveraged the Beat AML infrastructure to quickly pivot to treat patients with blood cancer who are infected with the coronavirus disease 2019 (COVID-19) virus. The trial is testing the drug acalabrutinib (Calquence), which is currently approved to treat several types of blood cancers. The trial is open to patients diagnosed with all types of blood cancers.

Additionally, LLS is also planning other precision medicine trials modeled after Beat AML, including LLS PedAL, a global precision medicine trial for children with relapsed acute leukemia, currently on track to launch in summer 2021, and Stop MDS, a master trial for patients with myelodysplastic syndromes.

1. STUDY IN NATURE MEDICINE SHOWS SUPERIOR OUTCOMES FOR PATIENTS IN LLS'S PARADIGM-SHIFTING BEAT AML CLINICAL TRIAL [news release]. Rye Brook, NY. Published October 26, 2020. Accessed October 28, 2020. https://www.lls.org/news/study-in-nature-medicine-shows-superior-outcomes-for-patients-in-llss-paradigm-shifting-beat-aml-clinical-trial?src1=182886&src2=

2. Burd A, Levine RL, Ruppert AS, et al. Precision medicine treatment in acute myeloid leukemia using prospective genomic profiling: feasibility and preliminary efficacy of the Beat AML Master Trial. 

Patients who participated in the Beat AML Master clinical trial were found to have superior outcomes with precision medicine, compared to patients with acute myeloid leukemia who opted for standard chemotherapy treatment.

Beat AML Master Clinical Trial Shows Promise for Precision Medicine in the Treatment of AML

Even though more effective and cost-efficient treatments for breast cancer are on the rise, researchers found that some patients, specifically Black women and patients without private insurance, are offered this therapy less often, according to a study published in the 

International Journal of Radiation Oncology Biology Physics

Recently, patients have undergone an alternative radiation treatment plan known as hypofractionated whole breast radiation rather than the standard breast-conserving cancer treatment of surgery followed by radiation therapy over a 5- to 6-week period. The treatment is just as effective at reducing the risk of a cancer returning, more cost-effective, and offers fewer side effects to patients and better breast restoration outcomes following treatment.

"We have identified patient populations at risk of not receiving a beneficial and more cost-effective therapy," lead author of the study, Alliric Willis, MD, FACS, said in a press release. "This research really illustrates that not all patients are being treated equally."

The investigation revealed that while the use of hypofractionated whole breast radiation to treat patients increased from around 25% in 2012 to around 67% in 2016, marked disparities in the patients being treated existed. Specifically, patients identifying as white were the most likely group to receive hypofractionated whole breast radiation, whereas African Americans were the least likely group to receive that treatment regimen.

The researchers utilized the National Cancer Database to examine data from almost 260,000 early-stage breast cancer patients over the age of 40 years who were diagnosed between 2012 and 2016. The cohort of patients had received radiation therapy following surgery. The researchers specifically compared demographics, tumor attributes and treatment facility characteristics of patients receiving hypofractionated whole breast radiation or tradiational radiation therapy.

More, socioeconomic status played a role in who received hypofractionated whole breast radiation treatment as well. The research found that patients with private insurance were more likely to receive hypofractionated whole breast radiation treatment than patients with public insurance or Medicaid. The researchers also found that patients who lived in areas with the highest income category zip codes were 25% more likely to receive hypofractionated whole breast radiation treatment than patients in the lowest income category zip codes.

"When we took all other factors into account, African American women were 15% less likely to be treated with hypofractionated whole breast radiation than white women," Willis said in a press release. "This demonstrates that even though treatment guidelines do not take race into account, race is a factor in breast cancer treatment."

Traditional radiation therapy consists of 25 to 30 daily radiation treatments for patients over a 5- to 6-week period following surgery. In recent years, patients have begun hypofractionated whole breast radiation treatment more often. This consists of higher radiation treatments per dose, resulting in only about 15 to 16 daily treatments for patients over a 3 to 4-week period.

The researchers suggest that this data will pave the way to reducing healthcare costs and increasing patient satisfaction for all patients with breast cancer.

"This tells us that there is a need to actively communicate information to healthcare providers about the spectrum of treatment options across all treatment facility types," Willis said. "Patients should have access to all treatment options no matter their race, socioeconomic background or where they seek care. Hopefully, our research will help to address gaps in provider education and extend this favorable treatment to all patients."

Not all patients are offered the same effective breast cancer treatment [news release]. Published September 30, 2020. 

https://www.eurekalert.org/pub_releases/2020-09/tju-nap093020.php

A study led by Jefferson researchers found that not all patients, specifically African American patients and women without private insurance, receive the same breast cancer treatment, specifically the beneficial and more cost-effective hypofractionated whole breast radiation therapy.