A rare pediatric disease designation has been granted by the FDA to DAY101 (formerly TAK 580 and MLN 2480) for the treatment of pediatric low-grade gliomas (pLGG), according to a press release from Day One.

There are currently no approved therapies or standard of care for pLGG, which, although rare, is the most common brain tumor diagnosed in pediatric patients. Should DAY101 receive a new drug application approval, Day One may receive a priority review voucher from the FDA, which will help to secure a priority review for marketing any application.

“Historical approaches to treating pLGG such as surgery, radiation, and chemotherapy are associated with significant acute and life-long adverse effects and new options are urgently needed,” Davy Chiodin, PharmD, chief development officer of Day One, said in a press release.

Single agent DAY101 has been investigated in over 250 patients and yielded a tolerable safety profile and promising anti-tumor activity in both pediatric and adult populations with certain 

 pathway alterations. Additionally, preliminary results from the phase 1 PNOC014 trial (NCT03429803), which examined the agent in gliomas and other tumors, indicated that of 8 patients with relapsed, 

 fusion–positive pLGG, 2 achieved a complete response, 3 achieved partial responses, 2 achieved prolonged stable disease, and one experienced progressive disease.

DAY101 will be examined in the pivotal phase 2 FIREFLY-1 trial (NCT04775485), which is currently enrolling pediatric, adolescent, or young adult patients who have a known 

The open label clinical trial will be comprised of approximately 60 patients who will be treated with DAY101 for a period of 26 cycles over the course of 24 months. DAY101 will be administered orally at the recommended phase 2 dose of 420 mg/m2 once weekly for each 28-day cycle. Patients are set to undergo radiographic evaluation at the end of every third cycle to evaluate disease progression.

DAY101 is an oral brain penetrant that is highly selective type 2 pan-RAF kinase inhibitor that was designed to target a key enzyme within the MAPK pathway.

The primary end point of the trial is overall response rate, with the secondary end points including safety and tolerability of DAY101 and relationship between pharmacokinetics and drug effects.

pLGG accounts for 30% to 50% of central nervous system tumors. 

 wild-type fusions are the most common cancer-causing genomic alterations, and they can also be found in both adult and pediatric solid tumors. The only BRAF inhibitors that are currently approved are active in patients who harbor 

mutations and have demonstrated limited activity in brain tumors. Additionally, they cannot be utilized in patients who have 

Some of the most common ways pLGG can impact patient quality of life is loss of vision and motor dysfunction. Although most patients with pLGG will survive their disease, those who cannot achieve a cure following surgery may face years of increasingly aggressive therapies that can have lasting effects on learning cognition and quality of life. Moreover, the indolent nature of pLGG means that patients may need to undergo many years of systemic therapy.

DAY101 was previously granted breakthrough therapy designation for the treatment of patients with pLGG harboring an active 

 alteration, need systemic therapy, and either progressed following prior treatment or have no other treatment options.

“DAY101 has the potential to become the first approved treatment option specifically for these patients. Receiving rare pediatric disease designation from the FDA underscores the critical value of our focus on pediatric indications at Day One and represents another significant milestone for the DAY101 program as we continue to enroll patients with pLGG in our pivotal phase 2 FIREFLY-1 study,” Chiodin concluded.

Day One receives FDA rare pediatric disease designation for DAY101 for the treatment of pediatric low-grad glioma. News Release. Day One. July 27, 2021. Accessed July 27, 2021. 

Articles

The phase 2 clinical trial is currently recruiting patients with pediatric low-grade glioma to be treated with DAY101 following a rare pediatric disease designation by the FDA. 

DAY101 Granted Rare Pediatric Disease Designation by the FDA for Pediatric Low-Grade Glioma

Radiation oncologists met with Congress to urge leaders to consider how the Medicare and Medicaid Services (CMS) proposal to make significant cuts to radiation oncology facilities could be detrimental to the survival of patients with cancer, according to a press release from the American Society for Radiation Oncology (ASTRO).

In 2021, 1.9 million people are anticipated to be diagnosed with cancer. This adds to an increasing number of late-stage cancer diagnoses caused by numerous delays in cancer screenings and detection due to the COVID-19 pandemic. This has led to a need for an "all doors open" treatment strategy in order to manage the increased number of patients with late-stage disease.

Over 100 oncologists met with medical physicists from 32 states and participated in 150 virtual meeting with lawmakers to emphasize the importance of keeping these facilities open. Oncologists noted 3 important points as to why the facilities need to remain open:

First, oncologists noted the importance of defending equitable access to care by reforming the Radiation Oncology Model and stabilizing Medicare rates. In September of 2020, the CMS proposed the creation of a Radiation Oncology Alternative Payment Model (RO Model) by January 2022.

 Further changes to the RO model were proposed on July 19, including slight revisions to the discount factor without addressing numerous concerns raised by both the radiation oncology community and a broad coalition of medical provider groups, patients, hospitals, health systems, and bipartisan members of Congress.

The community is anticipating notable reductions in the RO model due to Hospital Outpatient Prospective Payment System (HOPPs) rules and proposed cuts from the 2022 Medicare Physician Fee Schedule (MPFS), which led to a 8.75% cut to radiation therapy services that will largely affect rural and underserved communities, thus enabling further healthcare disparities. The cuts could lead to a 17% decline in physician reimbursement over the last decade, as well as a 22% reduction in high-value radiation treatment reimbursements.

ASTRO is requesting that the CMS reduce payment cuts or at least phase in reductions in order to preserve access to radiation oncology services and protect the financial viability of smaller practices. Additionally, the organization proposed a Health Equity Achievement in Radiation Therapy (HEART) payment in order to cover patient care navigation, which can help to manage healthcare disparities; this is not currently covered in Medicare fee schedules.

“CMS has singled out radiation oncology for payment cuts that put access to cancer care for Medicare beneficiaries in peril. By proposing to cut high-value radiation treatments by as much as 22% and proceeding with more than $160 million in reductions under the RO model, [the] CMS is jeopardizing the ability of the nation’s radiation therapy professionals to continue to provide essential care for their patients now and in the future," Thomas J. Eichler, MD, FASTRO, chair of the ASTRO Board of Directors, said in a press release.

Oncologists also emphasized the benefit of reducing prior authorization. In a survey that was conducted by ASTRO in August 2018 findings indicated that these authorizations are the greatest challenges in the field.

 During the pandemic, oncologists reported that prior authorizations worsened, and cancer treatment delays went up by 64%. Additionally, 66% of oncologists reported that their patients suffered negative results due to these delays. Moreover, a separate study that was conducted by Plos One indicated that each week of delayed treatment was associated with a 1.2% to 3.2% increase risk of cancer death.

Lastly, oncologists emphasized the importance of advocated for increased cancer research federal funding. Due to the pandemic, previous support for cancer research was upended due to the freeze on clinical trials and labs being closed. These elements resulted in an increase in cancer cases and deaths due to lapsed screening and availability to treatments. ASTRO emphasized the need for Congress to respond to the increased incidence of cancer with additional funding for various facilities such as National Institutes of Health and National Cancer Institute.

1. Radiation oncologists urge Congress to reverse proposed CMS cuts and create more equity in access to cancer treatments. News Release. ASTRO. July 26, 2021. Accessed July 27, 2021. 

2. Radiation oncology alternative payment model (RO Model). Press Kit. ASTRO. Accessed July 27, 2021. 

3. Prior authorization obstacles to cancer patient care. Press Kit. ASTRO. Accessed July 27, 2021. https://bit.ly/3740UVm

4.Khorana AA, Tullio K, Elson P, et al. Correction: time to initial cancer treatment in the United States and association with survival over time: an observational study. PLoS One. 2019;14(4):e0215108. doi:10.1371/journal.pone.0215108

Oncologists are trying to remedy the proposed cuts to radiation oncology facilities from the Centers for Medicare and Medicaid Services to lessen health disparities and improve equitable access to care. 

Radiation Oncologists Met With Congressional Leaders to Reverse CMS Cuts and Provide Equal Access to Care

The FDA has cleared an investigational new drug (IND) application for lanraplenib (GS-9876), allowing for a phase 1/2 trial that will examine the safety and efficacy of the agent in combination with gilteritinib (Xospata) in patients with relapsed/refractory, 

-positive acute myeloid leukemia (AML) to proceed, according to a press release from drug developer Kronos Bio.

Kronos Bio anticipates that the trial will begin during the fourth quarter of 2021. Lanraplenib was designed to improve pharmacokinetic and pharmacologic properties vs entospletinib (GS-9973), which is notably being evaluated in combination with standard-of-care chemotherapy in patients with newly diagnosed, 

-mutant disease as part of a phase 3 study (NCT02343939).

“This [lanraplenib] IND caps off an outstanding year for our [spleen tyrosine kinase (SYK)] portfolio, which we acquired just over a year ago. Since that time, we have nearly completed the integration of the [entospletinib] and [lanraplenib] programs with our systems, built out the requisite clinical, translational, regulatory, and manufacturing infrastructure for [lanraplenib] and [entospletinib] and had successful interactions with the FDA, both for the [entospletinib] phase 3 clinical trial, as well as for [lanraplenib] in relapsed/refractory 

-mututated [patients with] AML. The stage is now set to demonstrate the value of SYK inhibition for patients with this life-threatening disease,” Jorge DiMartino, MD, PhD, chief medical officer and executive vice president, clinical development of Kronos Bio, said in a press release.

The IND marks the first oncology indication for lanraplenib, which previously demonstrated tolerability in a clinical trial that included 250 patients with autoimmune diseases, as well as healthy volunteers. Moreover, pre-clinical findings indicated anti-leukemic activity with the agent in 

-mutant AML blood and bone marrow samples; lanraplenib proved to be comparable with entospletinib.

Lanraplenib’s pharmacokinetic profile allows for a once daily dosing regimen in a fed or fasted state and appears to be compatible with proton pump inhibitors. This suggests that the investigation therapy may be better suited to the chronic treatment paradigm than entospletinib.

The phase 1/2 trial examining lanraplenib will utilize a dose-escalation and -expansion cohort design, the first phase of which will evaluate the safety, pharmacokinetics, and anti-leukemic activity of the agent in an escalating once daily dose plus a standard dose of gilteritinib. 

 measurable residual disease negativity will also be examined in those who achieve a complete response in addition to assessing the predictive value of certain biomarkers that may be associated with clinical outcomes.

Investigators expect to have initial data from the first phase of the trial during the second half of 2022. After a recommended dose is selected by investigators, an expansion cohort of approximately 30 patients will be enrolled to better evaluate the safety of the investigational drug in addition to better understanding its anti-leukemic properties; these data are likely to emerge during the second half of 2023.

“Based on the existing clinical data and differentiated pharmacologic properties of [entospletinib] and [lanraplenib], we have designed a complementary development strategy that seeks to maximize the impact of both investigational medicines. [Entospletinib] is entering a registrational phase 3 clinical trial that may support its accelerated approval to treat newly diagnosed 

-mutated AML patients in combination with chemotherapy for a defined duration of treatment. [Lanraplenib’s] differentiated pharmacologic properties support its evaluation as a component of more extended combination dosing regimens with gilteritinib or venetoclax [Venclexta]/azacitidine, which are dosed to progression. We believe this precision oncology approach will allow us to systematically address patients with genetic mutations present in more than two-thirds of the AML patient population,” DiMartino concluded.

A second phase 1/2 trial is planned that will examine lanraplenib in combination with venetoclax (Venclexta) plus azacitidine in those with newly diagnosed, 

-mutant AML who are over the age of 75 and are not candidates for intensive induction chemotherapy. This trial is expected to yield data during the first half of 2023, with proof-of-concept data emerging in late 2023 or early 2024.

Kronos Bio announces FDA clearance of investigational new drug application for lanraplenib (LANRA) for treatment of patients with acute myeloid leukemia (AML). News release. Kronos Bio. July 27, 2021. Accessed July 27, 2021. https://bit.ly/2V9NzrI

A phase 1/2 trial featuring lanraplenib/gilteritinib in patients with FLT3-mutant acute myeloid leukemia will proceed following the FDA’s clearance of an investigational new drug application.

FDA Grants Clearance of Investigational New Drug Application for Lanraplenib in Combination With Gilteritinib for R/R FLT3+ AML

Ipilimumab (Yervoy) plus anti–PD-1/L1 therapy shows higher objective response rate (ORR) and longer progression-free and overall survival (OS) compared with ipilimumab alone for patients with advanced melanoma that is resistant to available PD-1/L1 inhibitors, according to a study published in 

At the median follow-up of 22.1 months, the ORR was 31% with ipilimumab plus anti–PD-1/L1 therapy versus 13% for ipilimumab monotherapy (

 <.0001). The median OS was 20.4 months (95% CI, 12.7-34.8) and 8.8. months (95% CI, 6.1-11.3) for the combination and ipilimumab monotherapy arms, respectively (HR 0.50; 95% CI, 0.38-0.66; 

 <.0001). The median progression-free survival (PFS) for ipilimumab plus anti–PD-1/L1 therapy was 3.0 months (95% CI, 2.6-3.6) compared with 2.6 months with ipilimumab alone (95% CI, 2.4-2.9; HR 0.69; 95% CI, 0.55-0.87; 

This study included 355 patients with unresectable stage III or metastatic melanoma. Patients were treated between February 1, 2011, and February 6, 2020, of whom 162 received ipilimumab monotherapy and 193 received ipilimumab plus anti–PD-1/L1 therapy.

In a post-hoc analysis, the 1-year OS rate was 58% (95% CI, 51%-66%) in the ipilimumab plus anti–PD-1/L1 group with 73 deaths compared with ipilimumab monotherapy at 38% (95% CI, 31%-48%) and 89 deaths. The 1-year PFS rates at the analysis were 24% (95% CI, 19%-32%) and 12% (95% CI, 8%-19%), respectively.

Investigators found that factors associated with longer better ORR and long OS with the combination included male sex, an ECOG performance status of 0, and normal lactate dehydrogenase.

 wild-type melanoma, stage IV M1c or M1d disease, or elevated lactate dehydrogenase experienced longer PFS and OS with ipilimumab plus anti–PD-1/L1 therapy compared with ipilimumab alone.

Grade 3 or greater treatment-related adverse events (TREAs) occurred in about a third of patients in both groups. The most common events were diarrhea, colitis, and increased alanine aminotransferase or aspartate aminotransferase. In the ipilimumab monotherapy group, 1 death occurred 26 days after the last treatment from a colon perforation.

Eleven patients had grade 3/4 TREAs on anti–PD-1/L1 monotherapy before the study treatment, 5 of whom experienced events of grade 3/4 severity on study. Relapses of the same AEs occurred in 4 patients, all with grade 3 events.

“This cohort study suggests a substantial clinical benefit with the ipilimumab plus anti–PD-1 treatment over ipilimumab monotherapy in patients with advanced melanoma resistant to anti-PD-(L)1; however, although the study is large, these results need to be interpreted with caution given the retrospective and non-randomized nature of this study,” wrote the study investigators who were led by Ines Pires da Silva, PhD.

Pires da Silva I, Ahmed T, Reijers ILM, et al. Ipilimumab alone or ipilimumab plus anti-PD-1 therapy in patients with metastatic melanoma resistant to anti-PD-(L)1 monotherapy: a multicentre, retrospective, cohort study. 

. 2021;22(6):836-847. doi:10.1016/S1470-2045(21)00097-8

Patients with PD-1 inhibitor-resistant melanoma who were treated with ipilimumab plus anti–PD-1 therapy saw significantly better long-term responses than those on ipilimumab alone. 


Retrospective Data Show Promise of Ipilimumab Plus PD-1/L1 Inhibitors in Resistant Melanoma 

The FDA granted approval to the supplemental biologics license application (sBLA) for pembrolizumab (Keytruda) as neoadjuvant therapy for patients with high-risk early-stage triple-negative breast cancer (TNBC) when given in combination with chemotherapy followed by single-agent use after surgery, according to the company responsible for the PD-1 inhibitor, Merck.

This decision by the FDA was supported by data from the phase 3 KEYNOTE-522 trial (NCT03036488) which examined the neoadjuvant regimen in the indicated patient population versus matched placebo and demonstrated a statistically significant event-free survival (EFS) benefit (HR, 0.63; 95% CI, 0.48-0.82; 

 = .00031) with active versus control therapy.

“Even when TNBC is diagnosed early, 30% to 40% of patients will suffer cancer recurrence after standard neoadjuvant chemotherapy and surgery,” Joyce O’Shaughnessy, MD, chair of Breast Cancer Research at Baylor University Medical Center of Texas Oncology, U.S. Oncology in Dallas, Texas, said in a press release. “Therefore, there is a high unmet need for new treatment options. Today’s approval is very welcome news and has the potential to change the treatment paradigm by now including an immunotherapy as part of the regimen for patients with high-risk early-stage TNBC.”

original sBLA for this indication was accepted by the FDA in July 2020

 with a prescription drug user fee act date set for March 2021.

 However, the agency decided to defer a decision regarding approval until data regarding EFS, one of 2 dual primary end points, were more mature.

 At that time, the other primary end point of pathologic complete response (pCR) had shown a statistically significant benefit of using pembrolizumab versus the control arm, with pCR rates of 64.8% versus 51.2%, respectively (HR, 0.63; 95% CI, 0.43-0.93).

At the median follow-up of 39 months, EFS data were made available showing that pembrolizumab produced a statistically significant EFS benefit compared with chemotherapy alone. For patients who were in the PD-L1–positive group, defined as those with a combined positive score of 1 or higher, there was a 33% reduced risk of EFS events with pembrolizumab compared with the placebo group (HR, 0.67; 95% CI, 0.49-0.92). In the PD-L1–negative group, patients receiving the pembrolizumab regimen had a reduced risk for EFS events by 52% compared with the placebo-chemotherapy group (HR, 0.48; 95% CI, 0.28-0.85).

accelerated approval of pembrolizumab plus chemotherapy for patients with locally advanced unresectable or metastatic PD-L1–positive TNBC

 was converted to regular approval based on confirmatory data in KEYNOTE-522. The data originally supporting this approval were from the double-blind, randomized, placebo-controlled phase 3 KEYNOTE-355 trial (NCT02819518).

According to Merck, KEYNOTE-355 recently demonstrated that first-line treatment with pembrolizumab in combination with chemotherapy results in a statistically significant and clinically meaningful improvement in overall survival compared with chemotherapy alone in patients with metastatic TNBC whose tumors expressed PD-L1.

“Triple-negative is a difficult-to-treat type of breast cancer that unfortunately is more common in the US in younger women and in Black women,” Vicki Goodman, MD, vice president of clinical research at Merck Research Laboratories, said in a press release. “We are proud to offer a new treatment option for patients faced with this challenging cancer. This neoadjuvant and adjuvant combination with Keytruda is the first immunotherapy regimen to be approved in high-risk early-stage TNBC, marking a meaningful milestone for the breast cancer community.”

In the KEYNOTE-522 trial, patients received pembrolizumab 200 mg every 3 weeks plus carboplatin and paclitaxel for 4 cycles followed by 4 additional cycles of preoperative pembrolizumab in combination with either doxorubicin or epirubicin plus cyclophosphamide every 3 weeks. After surgery, 9 cycles of pembrolizumab were administered every 3 weeks.

1. FDA Approves KEYTRUDA (pembrolizumab) for Treatment of Patients With High-Risk Early-Stage Triple-Negative Breast Cancer in Combination With Chemotherapy as Neoadjuvant Treatment, Then Continued as Single Agent as Adjuvant Treatment After Surgery. News release. Merck. Published July 27, 2021. Accessed July 27, 2021. https://bit.ly/2Vc0rgX

2. Merck Announces Two US Regulatory Milestones for KEYTRUDA (pembrolizumab) in Triple-Negative Breast Cancer (TNBC). News release. Merck. Published July 30, 2020. Accessed July 27, 2021. https://bwnews.pr/3f0tH1j

3. Merck receives complete response letter from US FDA for supplemental biologics license application (sBLA) for Keytruda (pembrolizumab) in high-risk early-stage triple-negative breast cancer (TNBC). News release. Merck. March 29, 2021. Accessed July 27, 2021. https://bit.ly/2QT45dx

4. FDA grants accelerated approval to pembrolizumab for locally recurrent unresectable or metastatic triple negative breast cancer. News release. FDA. Published November 13, 2020. Accessed July 27, 2021. https://bit.ly/3zxmBt0

5. Merck Announces Phase 3 KEYNOTE-355 Trial Met Primary Endpoint of Overall Survival (OS) in Patients with Metastatic Triple-Negative Breast Cancer Whose Tumors Expressed PD-L1 (CPS ≥10). News release. Merck. Published July 27, 2021. Accessed July 27, 2021. https://bit.ly/3i5yb8E

Based on results of the KEYNOTE-522 trial, the FDA approved pembrolizumab, the first immunotherapy for this indication, plus chemotherapy as neoadjuvant treatment for patients with early-stage triple-negative breast cancer.

FDA Approves Neoadjuvant Pembrolizumab Combination for Early TNBC Indication

At the 2021 American Society of Clinical Oncology Annual Meeting (ASCO), CancerNetwork® spoke with Julie Vose, MD, MBA, about the phase 3 ELEVATE CLL R/R trial (NCT02477696) concerning acalabrutinib (Calquence) versus ibrutinib (Imbruvica) for the treatment of patients with relapsed or refractory high-risk chronic lymphocytic leukemia (CLL). Vose focused on the toxicities associated with the treatments with the second-generation Brurton tyrosine kinase inhibitor potentially showing fewer toxic effects.

The study was a randomized, open-label, multicenter trial with the primary end point of progression-free survival and the secondary end points including the incidence of treatment-emergent infections of grade 3 or greater and overall survival.

One [abstract from ASCO 2021] that was very interesting to me was a trial that was in CLL, chronic lymphocytic leukemia, where patients were randomized to acalabrutinib versus ibrutinib for [the treatment of] CLL. This trial was a noninferiority trial so that the outcomes as far as responses were not that clinically significantly different [between arms]. What was different was the toxicities. We had always felt that possibly the second-generation Bruton tyrosine kinase inhibitors would be less toxic. This was the first trial that demonstrated that in a randomized trial, where the acalabrutinib, which is a second-generation [agent, caused] less atrial fibrillation and less hypertension. It did have a little bit higher [toxicity] in some categories, such as headach. I think it showed some of the changes that we felt were always there [we have now seen] demonstrated in a prospective randomized trial.

Byrd J, Hillmen P, Ghia P, et al. First results of a head-to-head trial of acalabrutinib versus ibrutinib in previously treated chronic lymphocytic leukemia. 

. 2021;39(suppl 15):7500. doi: 10.1200/JCO.2021.39.15_suppl.7500

Videos

CancerNetwork® sat down with Julie Vose, MD, MBA, at the 2021 American Society of Clinical Oncology Annual Meeting to talk about a clinical trial comparing acalabrutinib versus ibrutinib for patients with chronic lymphocytic leukemia. 


Julie Vose, MD, MBA, Discussed Toxicities Associated With Acalabrutinib or Ibrutinib for Chronic Lymphocytic Leukemia 

Each Monday, CancerNetwork® highlights the most important content from the previous week in oncology news.

This week, some of the focus is on treatment for triple-negative breast cancer, with research on leronlimab plus carboplatin showing a survival benefit, while the KEYNOTE-522 study showed an event-free survival improvement. Other updates include a comparison of GOZILA and COLOMATE studies for patients who have gastrointestinal malignancies and the FDA approval of belumosudil for those with chronic graft-versus-host disease.

Leronlimab Plus Carboplatin Appears to Yield Survival Benefit in Metastatic Triple-Negative Breast Cancer

Patients who were given leronlimab—a CCR5 antagonist designed to target multiple therapeutic markers—with carboplatin experienced a 72% decrease in cancer-associated macrophage-like cells after 30 days on the treatment. Investigators linked the decrease in cancer-associated macrophage-like cells to a 300% increase in mean progression-free survival, as well as a 450% increase in 12-month overall survival. Additionally, circulating tumor cells have appeared to be related to slowing progression and lower mortality.

Comparing GOZILA and COLOMATE: Ongoing Umbrella/Basket Trials Examining Genetic Testing in Gastrointestinal Malignancies

Circulating tumor DNA (ctDNA)-based next-generation sequencing (NGS) assays have advantages over classic tissue-based analyses because of their low invasiveness and availability of repeated sampling. Because of the low incidence of target gene alterations such as HER2 or 

 in gastrointestinal cancers, very large screening platforms are needed to develop genome-based clinical trials.

For those reasons, ctDNA-based screening studies are being actively conducted; among them are the GOZILA (Guardant Originates in Zipangu Liquid biopsy Arrival) study in Japan and the COLOMATE (COlorectal Cancer Liquid BiOpsy Screening Protocol for Molecularly Assigned ThErapy) study in the United States.

Event-Free Survival Improvement Noted in KEYNOTE-522 Study for Patients With Triple-Negative Breast Cancer

Investigators examined neoadjuvant pembrolizumab plus chemotherapy followed by single agent pembrolizumab in the adjuvant setting compared with the neoadjuvant chemotherapy and adjuvant placebo. The phase 3 trial represents the first time an anti–PD-1 therapy has yielded a statistically significant event-free survival result in this patient population.

At the 3-year follow-up, 84.5% patients in the pembrolizumab group were alive and did not experience an event compared with 76.8% of patients in the placebo group.

Key Presentations at ASCO 2021 Review Primary Prevention of Prostate Cancer in African American Men

At the 2021 American Society of Clinical Oncology Annual Meeting, CancerNetwork® spoke with Edmund Qiao, a fourth-year medical student from University of California San Diego and lead author of a study about prostate cancer prevention in African American men.

Belumosudil Granted Full Approval for Treatment of Chronic GVHD by FDA

This approval follows a priority review for the new drug application (NDA) that was granted back in November for the Rho-associated coiled-coil kinase 2 (ROCK2) inhibitor. The submission of the NDA was supported by data from the phase 2 ROCKstar (KD025-213) trial (NCT03640481) of belumosudil at 200 mg daily or twice daily in patients with previously treated cGVHD.

 to stay up to date on the latest in oncology.

Here are some of the important updates from CancerNetwork last week you might have missed in the world of oncology, featuring novel combinations for triple-negative breast cancer, genetic testing for gastrointestinal malignancies, and the FDA approval of belumosudil for chronic graft-versus-host disease.

CancerNetwork®’s Week in Review: July 26th, 2021

A perioperative chemotherapy regimen consisting of neoadjuvant docetaxel, oxaliplatin, and S-1 (DOS) followed by surgery and adjuvant S-1 was well tolerated and effective in a population of Korean patients with resectable locally advanced gastric cancer (LAGC), according to data from the phase 3 PRODIGY study (NCT01515748).

After a median follow-up of 38.6 months (interquartile range, 23.5-62.1) and a total of 183 progression-free survival (PFS) events, PFS was found to be significantly superior in the S-1 plus surgery and adjuvant DOS chemotherapy (CSC) arm compared with the up-front surgery followed by adjuvant S-1 (SC) arm (HR, 0.70; 95% CI, 0.52-0.95; 

 = .023). The 3-year PFS rate was 66.3% (95% CI, 59.6%-72.1%) vs 60.2% (95% CI, 53.6%-66.3%) in the CSC and SC groups, respectively.

“The phase 3 PRODIGY study has shown the benefit of adding neoadjuvant chemotherapy to standard D2 surgery plus adjuvant chemotherapy in Asian patients with resectable LAGC,” wrote the investigators. “The study met its primary end point: PFS was statistically significantly improved in CSC- versus SC- treated patients and HRs favored CSC in most subgroups.”

The research included 530 patients in the intent-to-treat population across 18 Korean hospitals between January 18, 2012, and January 2, 2017. Of this cohort, 266 patients were randomized to the CSC arm and 264 to the SC arm.

Overall, 89.9% of patients in the CSC group received all 3 cycles of DOS. Moreover, 16 patients who began neoadjuvant chemotherapy did not undergo surgery, with reasons including consent withdrawal (n = 6), death (n = 4), progressive disease (PD; n = 3) during neoadjuvant therapy (n = 3), lost to follow-up (n = 2), or adverse effects (AEs) before surgery (n = 1). From study enrollment to surgery, the median time between was 11.6 and 1.9 weeks in the CSC and SC groups, respectively.

Unlike PFS, the overall survival (OS) rate was not statistically significantly better for patients in the CSC group compared with those in the SC group (HR, 0.84; 95% CI, 0.60-1.19; 

 = .338). Expanded to 3-years, the OS rate was 74.2% (95% CI, 67.7%-79.6%) and 73.4% (95% CI, 67.0%-78.7%) in the CSC and SC groups, respectively.

Patients eligible for enrollment were between the ages of 20 to 75 years with an ECOG performance status of 0 to 1 and histologically confirmed primary locally advanced gastric or gastroesophageal junction adenocarcinoma amenable to curative resection.

Patients in the CSC group began treatment within 7 days of randomization, which included docetaxel at 50 mg/m2, oxaliplatin at 100 mg/m2 intravenously on day 1, and S-1 at 40 mg/m2 orally twice a day on days 1 through 14 every 3 weeks for 3 cycles.

A limitation of the data centered around the small HRs for both the PFS and absolute PFS data, with OS data also being immature. Moreover, other neoadjuvant chemotherapy options need to be explored outside of the treatment within PRODIGY.

“This trial establishes perioperative chemotherapy as an appropriate new standard-of-care option for patients with LAGC in Asia, analogous to the therapeutic approach commonly used in Western countries,” the investigators concluded.

Kang YK, Yook JH, Park YK, et al. PRODIGY: A phase III study of neoadjuvant docetaxel, oxaliplatin, and S-1 plus surgery and adjuvant S-1 versus surgery and adjuvant S-1 for resectable advanced gastric cancer. 

. Published online ahead of print, June 16, 2021. doi:10.1200/JCO.20.02914

Recent data indicated that the combination of neoadjuvant docetaxel, oxaliplatin, and S-1 followed by surgery and adjuvant S-1 was effective and tolerable in a population of Korean patients who had locally advanced gastric cancer.

Neoadjuvant Docetaxel, Oxaliplatin, and S-1 Plus Surgery and Adjuvant S-1 Effective in Korean Population With Advanced Gastric Cancer

Black and low-income patients with cancer were found to be at a higher risk of having severe complications after being diagnosed with COVID-19, according to findings from a retrospective observational cohort study that was published in 

Findings from the study indicated that patients who lived in a zip code where the median household income was below $30,000 were twice as likely to be hospitalized for pneumonia, fluid balance disorders, cough, respiratory failure, or acute renal failure. Moreover, patients who lived in an area where the median household income was below $30,000 were more likely to be diagnosed with COVID-19 via International Classification of Diseases codes alone (62%) vs areas with a median household income of more than $30,000 (49%). Those with COVID-19 and active cancer or who reside in zip codes with a median household income of less than $30,000 had a higher incidence of death, hospital admission, and use of invasive respiratory support.

Black patients were more likely to be admitted for breathing abnormalities, pneumonia, fluid balance disorders, cough chronic kidney disease, and fever than any other group included in the study. Black patients were also more likely to undergo invasive respiratory support vs other racial and ethnic groups.

“The data analyzed demonstrates health disparities related to both race and income that are multi-factorial and already well-recognized in the US,” Clara Hwang, MD, a medical oncologist at Henry Ford Cancer Institute and principal investigator of the study, said in a press release.

 “Our hope is [that] these findings will help inform the care provided for those who are at a higher risk of complications or death from COVID-19, and lead to continued research that will help us better understand why this disproportionate effect on Black patients exists.”

In the study, investigators analyzed the clinical outcomes of patients who had been diagnosed with COVID-19 in a hospital setting, as well as having active cancer or a history of cancer. Investigators analyzed data from 146,702 patients with cancer who had been diagnosed between 2015 to 2020, from which 1267 cases of COVID-19 were identified from February 2020 to July 2020.

The primary outcome of the study was all cause mortality, with key secondary outcomes including hospitalization and utilization of inpatient invasive mechanical ventilation.

Additional findings from the study indicated that male patients with COVID-19 and cancer were more likely to have breathing abnormalities than female patients. Conversely, female patients had a lesser chance of having active cancer, comorbidities, or the need to take antihypertensive medications. Female patients were also more likely to be younger with a lower risk of death, hospitalization, and invasive respiratory support.

“The findings from this study show that patients with cancer are more vulnerable to the effects of COVID-19, especially those with comorbidities and cancer that has been diagnosed in the past 12 months,” Shirish Gadgeel, MD, division head of Hematology/Oncology at Henry Ford Cancer Institute, and co-author of the study, said. “We found that people with cancer who were diagnosed with COVID-19 were more likely to have other chronic underlying illnesses compared [with] patients with cancer without COVID-19, such as chronic conditions affecting the kidneys, heart, lungs and blood vessels. Our findings indicate older people with cancer were more likely to die from COVID-19, which is consistent with what has been observed among those without cancer.”

In a study presented at the 2020 American Society of Clinical Oncology Quality Care Symposium

, Black patients who were diagnosed with cancer were found to be more likely to have severe complications from COVID-19.

 The study examined 557 patients who tested positive for COVID-19 after they had at least 1 visit to the cancer center in the last year. Among the patients who were included in the study, 325 (58%) were female, 79 (14%) were Black, and 225 (40%) had 2 or more comorbidities. Additionally, investigators identified gastrointestinal cancer (n = 105) as the most common disease type.

From this group, 56 patients went to the emergency department, 26% of whom were Black (

 = .002). Among patients who required an inpatient hospital visit (n = 96), 19% were Nlack (

 = .13). Investigators also examined comorbidities, demographics, and cancer variables and reported that Black race was identified as being independently associated with higher odds of hospitalization (OR, 2.19; 95% CI, 1.2-3.8).

1. Hwang C, Izano MA, Thompson MA, et al. Rapid real-world data analysis of patients with cancer, with and without COVID-19, across distinct health systems. 

2. Study of cancer patients and COVID-19 highlights health disparities. News Release. Henry Ford Health Systems. July 22, 2021. Accessed July 22, 2021. 

3. Pandya C, Mwesigwa S, Dougherty DW. Racial differences in hospitalizations associated with COVID-19 in patients with cancer. 

. 2021;38(suppl 29):122-122. doi:10.1200/JCO.2020.38.29_suppl.122

Patients with cancer who are Black or live in low-income areas were found to be at a higher risk of COVID-19 complications, according to recent findings.

Black and Low-Income Individuals With Cancer May Be at a Higher Risk for COVID-19 Complications

At the 2021 American Society of Clinical Oncology (ASCO) Annual Meeting, CancerNetwork® sat down with Robert A. Figlin, MD, professor of Biomedical Sciences and Medicine, Steven Spielberg Family Chair in Hematology-Oncology, and deputy director of Cedars-Sinai Cancer, to highlight the potential importance of adjuvant immunotherapy in bladder cancer. As previous research has identified significant benefit with this modality, Figlin emphasizes the importance of discovering the best role for immunotherapy in this patient population.

Concomitant with ASCO was a recent New England Journal of Medicine article talking about immunotherapy in the invasive bladder cancer population, [which demonsted] a substantial and significant benefit [to therapy]. We should start to think about adjuvant immunotherapy for bladder cancer. [This would be] primarily diseases of the bladder, not necessarily the ureter or the kidney. As we continue to expand and search for appropriate roles for immunotherapy, we should not forget other diseases like bladder cancer in that setting.

Bajorin DF, Witjes JA, Gschwend JE, et al. Adjuvant Nivolumab versus Placebo in Muscle-Invasive Urothelial Carcinoma. N Engl J Med. 2021;384(22):2102-2114. doi:10.1056/NEJMoa2034442

Robert A. Figlin, MD, discusses the potential role of adjuvant immunotherapy for patients with bladder cancer.

ONCOLOGY Vol 35, Issue 7 | August 2021

Clinical Trials in Progress

Clinical Trials in Progress: GOZILA

Original Research

Comparing GOZILA and COLOMATE: Ongoing Umbrella/Basket Trials Examining Genetic Testing in Gastrointestinal Malignancies

Review Article

Level of Scientific Evidence Underlying the National Comprehensive Cancer Network Clinical Practice Guidelines for Hematologic Malignancies: Are We Moving Forward?

Review Article

Profilin 1 Protein and Its Implications for Cancers

Review Article

Combination Therapy With Immune Checkpoint Inhibitors in Urothelial Carcinoma: Current Data and Future Outlook

Case Study

Median Lobe Urethral Embolus After Focal Ablation of Gleason 7 Prostate Cancer

Clinical Quandaries

Advanced Penile Cancer Presenting With Renal Failure

Editorial

The Future of Telehealth for Hematology/Oncology Care