Rose McNulty

Data gathered by Cardinal Health Specialty Solutions revealed roadblocks community oncology practices encounter when trying to navigate payer approvals for CAR T-cell therapy.

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A recent paper in Nature Cancer outlines a novel strategy for overcoming barriers to CAR T-cell therapy in glioblastoma by pretreating the vascular microenvironment.

Moving a Step Closer to Using CAR T-Cell Therapy in Solid Tumors

At the recent meeting of the American Society of Hematology, results from several studies involved the use of chimeric antigen receptor (CAR) T-cell therapy in multiple myeloma. 

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Karl Kilgore, PhD, a senior research scientist at Avalere Health, discusses Medicare data that offer insights on the overall costs of CAR T-cell therapy relative to transplants.

Real-World Data Offer Good News for CAR T-Cell Therapy

City of Hope's Dr. Tanya Siddiqi offers an update on a new chimeric antigen receptor (CAR) T-cell therapy awaiting approval from the FDA.

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The vice president for Clinical Services at OneOncology describes challenges and opportunities for chimeric antigen receptor (CAR) T-cell therapy in the community practice setting.

OneOncology’s Duncan Allen, MHA, Discusses Bringing CAR T-cell Therapy to the Community Setting

From the Academic Center to Community Practice 

Articles

CAR-T Spotlight

Combination nivolumab and ipilimumab has demonstrated efficacy in the first-line setting for 

 (NSCLC), and recently published results from the ongoing CheckMate 9LA trial (

) show that adding a limited course of chemotherapy to the combination treatment is effective and tolerable.

The combination of nivolumab plus ipilimumab and chemotherapy was approved by the FDA on May 26, 2020, as a first-line treatment for metastatic or recurrent NSCLC cancer with no epidermal growth factor receptor or anaplastic lymphoma kinase genomic tumor aberrations. The application was approved based on CheckMate 9LA data 2 months ahead of schedule after being granted priority review and fast track designation by the FDA.

The randomized, open-label, phase 3 CheckMate 9LA trial enrolled 1150 patients at 103 hospitals in 19 countries between August 24, 2017 and January 30, 2019. Patients aged 18 years or older with treatment-naïve stage IV or recurrent NSCLC and an Eastern Cooperative Oncology Group performance status of 0-1 were eligible.

Of the 1150 enrolled patients, 719 were randomized to receive either 4 cycles of chemotherapy alone (n = 358) or nivolumab (360 mg intravenously every 3 weeks) plus ipilimumab (1 mg/kg intravenously every 6 weeks) with 2 cycles of histology-based, platinum doublet chemotherapy (n = 361). The primary end point was overall survival (OS).

At an interim analysis after a median follow-up of 9.7 months, OS in the combination therapy cohort was significantly longer than in the chemotherapy control group (median OS 14.1 months [95% CI, 13.2-16.2] vs 10.7 months [95% CI, 9.5-12.4], respectively). At an additional 3.5 months of follow-up (median 13.2 months), the nivolumab and ipilimumab plus chemotherapy cohort had a median OS of 15.6 months (95% CI, 13.9-20), while the chemotherapy alone group had a median OS of 10.9 months (95% CI, 9.5-12.6).

Neutropenia, anemia, diarrhea, increased lipase, and asthenia were the most common grade 3 or 4 treatment-related adverse events (TRAEs). In the combination therapy group, 7% had grade 3 or 4 neutropenia, 6% had anemia, 4% had diarrhea, 6% saw increased lipase, and 1% had asthenia. In the chemotherapy alone group, those grade 3-4 TRAEs occurred in 9%, 14%, 1%, 1%, and 2% of patients, respectively.

Serious TRAEs of any grade affected 30% of patients in the combination therapy group, compared with 18% of the control group. There were 7 treatment-related deaths in the nivolumab and ipilimumab plus chemotherapy cohort and 6 in the control group.

The authors concluded that the data support using nivolumab plus ipilimumab with 2 cycles of chemotherapy as a first-line treatment option for advanced NSCLC. Those patients saw significant improvement in OS versus patients given chemotherapy alone, and the risk-benefit profile was favorable, they wrote.

1. Paz-Ares L, Ciuleanu TE, Cobo M, et al. First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial. 

Published online January 18, 2021. doi:10.1016/S1470-2045(20)30641-0

2. FDA approves nivolumab plus ipilimumab and chemotherapy for first-line treatment of metastatic NSCLC. U.S. Food & Drug Administration. Published May 27, 2020. Accessed January 22, 2021. 

https://www.fda.gov/drugs/drug-approvals-and-databases/fda-approves-nivolumab-plus-ipilimumab-and-chemotherapy-first-line-treatment-metastatic-nsclc

Recently published results show that adding a limited course of chemotherapy to nivolumab plus ipilimumab in the first-line setting for non-small cell lung cancer is effective and tolerable. 

First-line Nivolumab and Ipilimumab Plus Chemotherapy Improves OS in NSCLC

A recent study from the University of Texas MD Anderson Cancer Center found that men with localized 

 might benefit from following a Mediterranean-style diet over the course of their disease.

 emphasizes eating plenty of vegetables; getting protein from sources like fish, poultry, beans, and eggs; eating moderate portions of dairy; and limiting red meat consumption. The 

, homed in on the diet as a potentially outcome-changing eating strategy because it has been shown to have an array of protective effects when followed consistently. Research has linked the Mediterranean diet to many potential health benefits, including a lower risk of heart disease, lower cholesterol and blood pressure, and even a decreased risk of developing cancer.

To find out whether the Mediterranean diet might benefit men with localized prostate cancer, researchers had 410 patients with newly diagnosed prostate cancer on active surveillance complete a baseline food frequency questionnaire with 170 items. They calculated a Mediterranean diet score based on 9 energy-adjusted food groups and categorized the patients based on high, medium, or low adherence to the diet; they then looked for associations between diet score and progression-free survival (PFS).

Patients underwent confirmatory biopsies at the start of the study and had Gleason Grade Group (GG) 1 or 2 localized prostate cancer. They were monitored biennially, and PFS was defined as an increase in GG score. Cox proportional hazard models were used to adjust for other known risk factors in the analysis.

Men whose diets included more fruits, vegetables, legumes, grains, and fish  were less likely to have their cancer advance to the point where active treatment was necessary. At a median follow-up of 36 months, the researchers found that for every 1-point increase in Mediterranean diet score, participants had a 12% lower risk of disease progression (HR per 1-point increase, 0.88; 95% CI, 0.77‐1.01).

In non-White men, the effect was even more pronounced (HR, 0.64; 95% CI, 0.45‐0.92; 

 = .07). Of the men in the overall cohort, 15% were had diabetes and 44% used statins. In men without diabetes, the HR was 0.82 (95% CI, 0.71‐0.96; 

“Men with prostate cancer are motivated to find a way to impact the advancement of their disease and improve their quality of life,” lead study author Justin Gregg, MD, assistant professor of urology at MD Anderson, said in a 

 “A Mediterranean diet is noninvasive, good for overall health, and, as shown by this study, has the potential to affect the progression of their cancer.”

The analysis was limited by a low number of events, with only 76 men seeing their cancer progress during the study. Disease risk was also low in most of the cohort, so larger and more diverse studies that include men with higher-risk disease are warranted to confirm the potential benefits of the Mediterranean diet, the authors wrote.

In cases where patients with low-risk disease and their physicians opt for active surveillance, exploring the potential of lifestyle changes to manage progression is of interest given the known quality-of-life adverse effects of active treatment for prostate cancer and cancer in general.

“The Mediterranean diet consistently has been linked to lower risk of cancer, cardiovascular disease, and mortality,” senior author Carrie Daniel-MacDougall, PhD, an associate professor of epidemiology at the University of Texas, said in the statement. “This study in men with early-stage prostate cancer gets us another step closer to providing evidence-based dietary recommendations to optimize outcomes in cancer patients, who, along with their families, have many questions in this area.”

1. Gregg JR, Zhang X, Chapin BF, et al. Adherence to the Mediterranean diet and grade group progression in localized prostate cancer: an active surveillance cohort. 

Published online January 7, 2021. doi:10.1002/cncr.33182

2. Diet review: Mediterranean diet. Harvard T.H. Chan School of Public Health. Updated December 2018. Accessed January 22, 2021. 

https://www.hsph.harvard.edu/nutritionsource/healthy-weight/diet-reviews/mediterranean-diet/

3. What is the Mediterranean diet? American Heart Association. Updated January 9, 2021. Accessed January 22, 2021. 

https://www.heart.org/en/healthy-living/healthy-eating/eat-smart/nutrition-basics/mediterranean-diet

4. Mentella MC, Scaldaferri F, Ricci C, Gasbarrini A, Miggiano GAD. Cancer and Mediterranean diet: a review. 

Published online September 2, 2019. doi:10.3390/nu11092059

5. Mediterranean diet may decrease risk of prostate cancer progression for men on active surveillance. News release. MD Anderson Cancer Center. January 7, 2021. Accessed January 22, 2021. 

https://www.mdanderson.org/newsroom/mediterranean-diet-may-decrease-risk-of-prostate-cancer-progression-for-men-on-active-surveillance.h00-159457689.html#.YAbliuVv8zE.mailto

A recent study from the University of Texas MD Anderson Cancer Center found that men with localized prostate cancer on active surveillance might benefit from following a Mediterranean-style diet.

Mediterranean Diet Might Benefit Low-Risk Prostate Cancer Patients 

Magnetic resonance imaging (MRI) is often used in the diagnosis and management of 

, but the method frequently underestimates tumor size, a 

 from the UCLA Jonsson Comprehensive Cancer Center found. 

, aimed to assess radiologic tumor size vs actual pathological tumor size in patients with 

 and to identify predictors of pathological tumor size. 

Researchers assessed a cohort of 441 men with biopsy-proven prostate cancer and 3 or higher index lesions based on the Prostate Imaging Reporting and Data System version 2 (PI-RADSv2) who later underwent radical prostatectomy. They defined radiologic tumor size as the maximum tumor diameter determined by the MRI and compared those measurements to those found in the whole-mount histopathology after resection.

The analysis included 461 lesions from the 441 patients identified. The mean radiologic tumor size was 1.57 cm, whereas the mean pathological tumor size was 2.37 cm. Although tumor size was consistently underestimated in the radiologic setting, tumors that were smaller and had lower 

 scores tended to be further underestimated than others.

In cases where tumors were categorized as grade 5 on the 

(GG), pathological tumor size was larger compared with GG grade 1 tumors, with a mean change of 0.37 cm (

= .014). Lesions rated 5 on the PI-RADSv2 index also had pathological tumor sizes larger than PI-RADSv2 4 lesions, with a mean change of 0.26 (

= .006). Tumors with higher prostate-specific antigen density were also larger.

Overall, there was not much correlation between radiologic tumor measurements and pathological tumor size in the cohort. The researchers saw correlation coefficients ranging from 0.1 to 0.65. Inaccurate tumor measurements can make it difficult for physicians to see where the outer edges of the tumor end and healthy tissue begins, potentially leading to insufficient treatment when the measurements are underestimated.

“Multiparametric magnetic resonance imaging frequently underestimates pathological tumor size and the degree of underestimation increases with smaller radiologic tumor size and lower PI-RADSv2 scores,” the authors concluded.

For the treatment of smaller tumors and those rated low on the PI-RADSv2 scale, they suggest that a larger ablation margin might be necessary as physicians estimate focal therapy treatment margins.

Pooli A, Johnson DC, Shirk J, et al. Predicting pathological tumor size in prostate cancer based on multiparametric prostate magnetic resonance imaging and preoperative findings. 

. 2021;205(2):444-451. doi:10.1097/JU.0000000000001389

Magnetic resonance imaging (MRI) is often used in the diagnosis and management of prostate cancer, but the method frequently underestimates tumor size, a study in the Journal of Urology shows. 

Rose McNulty

Articles

CAR-T Spotlight

First-line Nivolumab and Ipilimumab Plus Chemotherapy Improves OS in NSCLC

Mediterranean Diet Might Benefit Low-Risk Prostate Cancer Patients

Prostate Cancer Tumor Size Often Underestimated by MRI, Study Finds