Managed Care Updates: Spring 2023

Humana Leaving Commercial Business, Will Focus on Government-Funded Programs

Humana will move out of commercial plans during the next 18 to 24 months to focus on government-funded programs and specialty businesses. Included in the business Humana is leaving are all fully insured, self-funded, and Federal Employees Health Benefits medical plans.

The company announced the move February 23, 2023, after a strategic review determined the Employer Group Commercial Medical Products business was no longer able to “sustainably meet the needs of commercial members over the long term,” according to a news release.¹

“This decision enables Humana to focus resources on our greatest opportunities for growth and where we can deliver industry-leading value for our members and customers,” Bruce D. Broussard, Humana’s president and CEO, said in a statement. “It is in line with the company’s strategy to focus our health plan offerings primarily on government-funded programs [Medicare, Medicaid, and Military] and specialty businesses, while advancing our leadership position in integrated value-based care and expanding our CenterWell health care services capabilities.”

In late 2022, Humana announced that it was expanding CenterWell, which offers payer-agnostic, senior-focused primary care services. The plan to expand CenterWell includes adding centers in Indiana, Kentucky, Louisiana, Mississippi, Nevada, North Carolina, South Carolina, Tennessee, Texas, and Virginia.²

As of September 30, 2022, Humana had 8.7 million Medicare members in all 50 states, as well as Washington, DC, and Puerto Rico. In addition, more than half (5.1 million) of those members were enrolled in a Medicare Advantage (MA) plan.³

News of Humana’s move came days after a new report highlighted the growth of MA plans. Health care consulting group Chartis found that although MA growth had slowed this year compared with the 3 previous years, overall participation in the program still grew by 5.5%, or an additional 1.5 million beneficiaries.⁴ A record 29.5 million individuals are now enrolled in MA plans, with 46% of all Medicare beneficiaries enrolled in MA. In 2019, only 37% of all Medicare beneficiaries were in MA plans.

In the Chartis report, Humana was mentioned as one of the drivers of MA growth. UnitedHealthcare led the way, accounting for 55% of market growth, Chartis reported, followed by Humana, which accounted for 23% of growth. From 2022 to 2023, Humana’s enrollment in MA grew 6.8%.³

“While these 2 health plans often led in years past, this increase reflects considerably more concentrated performance,” according to the report.
Chartis also highlighted the importance of CMS’ star ratings on enrollment. Health plans with increasing quality had enrollment gains and, overall, 73% of MA beneficiaries are in health plans that have 4 stars or better. Similarly, Humana reported that 96% of Humana’s MA members are enrolled in plans that have 4 stars or above.⁵

The fact that MA plans cover extra benefits—like dental, vision, fitness memberships, and more—makes them very attractive to Medicare beneficiaries and has contributed to the popularity and rapid growth of these plans, Dennis Scanlon, PhD, professor of health policy and administration, Pennsylvania State University, told The American Journal of Managed Care® in an interview.

Despite their popularity, there are downsides to MA plans. Kaiser Family Foundation found that in 2022, 99% of MA enrollees were in plans requiring prior authorization (PA) for some services.⁶ PA is often required for expensive services, such as Part B drugs and skilled nursing facility stays, and also for the majority of enrollees for some of those extra benefits, such as dental services and hearing and eye examinations.

“In contrast to Medicare Advantage plans, traditional Medicare does not generally require prior authorization for services and does not require step therapy for Part B drugs,” the authors noted.

Oncologists have increasingly cited challenges with PA and step therapy, which is permitted in MA plans, as causes of delays in getting patients guideline-directed therapy for cancer treatment. 

References
1. Humana to exit employer group commercial medical products business. News release. Humana. February 23, 2023. Accessed February 23, 2023. http://bit.ly/3KFDWbZ
2. CenterWell Senior Primary Care 2023 expansion plan includes new markets of Indiana, Mississippi, and Virginia. News release. Humana. November 16, 2022. Accessed February 23, 2023. http://bit.ly/41qrLpp
3. U.S. News and World Report names Humana 2023 best overall Medicare Advantage plan company. News release. Humana. November 10, 2022. Accessed February 23, 2023. http://bit.ly/3Z5bYL0
4. Herro N, Pathiyal A, Wokurka J. In a shifting market, Medicare Advantage shows continued—but decelerating—growth. Chartis. February 21, 2023. Accessed February 23, 2023. https://www.chartis.com/insights/shifting-market-medicare-advantage-shows-continued-decelerating-growth
5. 96% of Humana’s Medicare Advantage members are in contracts rated 4-star or above for 2023; 66% are in contracts rated 4.5-star or higher. News release. Humana. October 7, 2022. Accessed February 23, 2023.
http://bit.ly/3malrlX
6. Freed M, Fuglesten Biniek J, Damico A, Neuman T. Medicare Advantage in 2022: premiums, out-of-pocket limits, cost sharing, supplemental benefits, prior authorization, and star ratings. Kaiser Family Foundation. August 25, 2022. Accessed February 23, 2023. http://bit.ly/3Z57KTR

Immune Signature Could Help Tailor Treatment Choices in NSCLC

A new analysis of immune-related genes in non–small cell lung cancer (NSCLC) has resulted in the identification of an immune signature that investigators say could help clinicians better understand an individual patient’s prognosis.

The report, published in Frontiers in Oncology, could also help guide clinical care, the authors said.

NSCLC is the most common type of lung cancer, and lung adenocarcinoma (LUAD) has become the most common subtype of NSCLC. Patients with NSCLC have a 5-year survival rate of just 18%, wrote the study authors.

One of the biggest advances in the treatment of NSCLC has been the development of immune checkpoint inhibitors, which target immune checkpoints such as PD-1 and PD-L1, among others. However, the investigators noted that only about 1 in 5 patients with NSCLC respond to anti–PD-1/PD-L1 therapy, a problem that may be caused by the heterogeneity of the cancer type and its tumor microenvironment.

“Thus, regarding their prognostic potential in LUAD, the molecular events of tumor cell immunocyte interactions in LUAD microenvironments need to be further summarized, and the expression level of immune-related genes (IRGs) in LUAD needs to be comprehensively explored,” they wrote.

They set out to do just that. First, they extracted the profiles of IRGs for patients with NSCLC from 3 databases. Next, they constructed coexpression modules and identified the hub genes of the modules that had the highest correlations with tumor samples. They then analyzed those results to see which hub genes seemed to play a role with tumor progression and cancer-associated immunology. Finally, they used LASSO Cox regression analyses to screen prognostic signatures and develop a risk model, they said.

“Functional analysis showed that immune-related hub genes were involved in the migration, activation, response, and cytokine–cytokine receptor interaction of immune cells,” they wrote.

Most of the hub genes had high frequencies of amplifications, with MASP1 and SEMA5A having the highest rates, they said. M2 macrophages and naïve B cells had a significantly negative correlation, they said, whereas CD8-positive T cells and activated CD4-positive memory T cells, naïve B cells, and plasma cells had a positive correlation, they noted.

In terms of patient outcomes and overall survival (OS), the authors found several insights. “Our results indicated that a high level of resting mast cell infiltration was associated with better prognosis, whereas a high level of activated mast cells was significantly related to worse OS,” they said.
The authors were able to develop and verify a prognostic immune signature.

They said unsupervised hub gene clustering was used to create 2 NSCLC subgroups, and those 2 subgroups had distinct differences in tumor immune dysfunction and exclusion scores and in their sensitivity to several common cancer therapies.

They said their model would need to be validated using a larger number of clinical samples, but that the subgroups identified in their study may help clinicians choose the most appropriate therapeutic strategy.

“These findings suggested that our immune-related genes can provide clinical guidance for the diagnosis and prognosis of different immunophenotypes and facilitate the management of immunotherapy in NSCLC,” they concluded. 

Reference
Han S, Jiang D, Zhang F, et al. A new immune signature for survival prediction and immune checkpoint molecules in non-small cell lung cancer. Front Oncol. 2023;13:1095313. doi:10.3389/fonc.2023.1095313

Study Identifies FGFR3 as Biomarker for Superior Outcomes in NSCLC

New research has identified a potential new biomarker for overall survival (OS) in patients with non–small cell lung cancer (NSCLC).

The study, published in Journal of Thoracic Disease, found that the expression of fibroblast growth factor receptor 3 (FGFR3) was associated with patient outcomes.

Study authors noted that FGFR3 is involved in a variety of processes including cell proliferation, differentiation, and migration. Previous studies have identified alterations in FGFR3 in cases of NSCLC, but they have come to varying conclusions about the frequency of the alterations.

“To date, no data are available on the distribution rates for FGFR3 expression and mutation, its relation to clinicopathological characteristics, and clinical outcomes in NSCLC,” they explained.

The authors decided to use immunohistochemistry to evaluate FGFR3 protein expression in 116 tissue samples from patients with NSCLC and then use Sanger sequencing to probe the mutation status of exons 7, 10, and 15. They then analyzed those results to see how they correlated with outcomes in the 86 patients for whom complete clinical data were available.

Among the 86 cases included in the analysis, FGFR3 was immunoreactive in 26 cases. FGFR3 was positively expressed in 84.6% of the 39 adenocarcinoma cases in the data set, but it was only positively expressed in 15.4% of the 47 squamous cell carcinoma cases.

In terms of mutations, the investigators found a low frequency rate. Mutations were present in just 2 of 72 cases—1 adenocarcinoma case and 1 squamous cell carcinoma case—and both had the T450M mutation. Further, both were novel mutations in exon 10; no mutations were found in exons 7 or 15.

When investigators compared their findings to patient outcomes, they found high FGFR3 expression was associated with better OS and better disease-free survival (DFS). Patients in the high-FGFR3 group were also more likely to be female, nonsmokers, and at an earlier T stage.

“The results of the survival analysis revealed the patients with high FGFR3 expression levels had better OS, which suggests that lower or reduced FGFR3 expression levels may enhance NSCLC progression, while FGFR3 overexpression may attenuate NSCLC progression,” they wrote.

The investigators noted that FGFR3 expression has been linked with a poorer prognosis in other types of cancer, including muscle-invasive bladder carcinoma and breast cancer, and that there are a number of potential reasons for the apparent contradiction.

“In the present study, we only included the patients with surgically resectable NSCLC at the I-IIIA stage, and the favorable prognostic role of FGFR3 may only occur in patients with early-stage NSCLC,” they said.

The authors added that the rate of FGFR3 expression was significantly higher among patients with adenocarcinoma, and patients with high FGFR3 expression tended to have higher EGFR mutation rates. Thus, patients with high FGFR3 expression were more likely to be treated with EGFR tyrosine kinase inhibitors.

“Therefore, it is speculated that patients with high FGFR3 expression have longer OS and DFS and are closely associated with higher EGFR mutations,” they said. “However, the mechanistic actions still need to be further investigated.”

The authors cautioned that their study is preliminary and based on a single center in a single country, and thus may not be generalizable to the entire NSCLC population. Still, they said their initial findings suggest FGFR3 may be a useful biomarker in this cancer type. 

Reference
Lin YE, Long HD, Chen CC, et al. High expression of FGFR3 predicts a better prognosis for patients with non-small cell lung cancer in a Chinese population. J Thorac Dis. 2023;15(1):101-111. doi:10.21037/jtd-22-1523

Surgical Quality Metric Adherence Substantially Improves Outcomes in Early NSCLC

Adherence to intraoperative quality metrics leads to a substantial improvement in the outcomes of patients with early-stage non–small cell lung cancer (NSCLC) following curative-intent resection, according to a new study published in JAMA Surgery.

The report found patients receiving care through the Veterans Health Administration (VHA) whose physicians followed most of the 13 intraoperative quality metrics had a median overall survival (OS) more than double that of patients whose physicians followed 5 or fewer metrics.

The preferred treatment for fit patients with early-stage NSCLC is surgical resection, and most guidelines for surgery recommend following a set of modifiable, process-based quality metrics, wrote the study authors.

These metrics include timely surgery, receipt of anatomic resection, a minimally invasive approach, negative surgical margin, and adequate lymph node sampling,” the authors wrote.

Still, despite evidence that following these metrics improves patient outcomes, widespread adoption of the guidelines has been insufficient,
they noted.

“Standardization of lung cancer treatment quality within the VHA may therefore have a disproportionate impact on early-stage NSCLC outcomes among veterans and provide a road map for implementation in the general US population,” they wrote.

To demonstrate the effects of following quality metrics, the authors turned to the VHA, which they said has patterns of lung cancer care and outcomes similar to those of the general population. They then developed a scoring system to see how closely providers were following the quality metrics and compared those scores with patient outcomes.

The investigators retrospectively compiled a cohort of 9628 veterans who underwent resection for clinical stage I NSCLC between 2006 and 2016. The patients had a mean age of 67.6 years, and most (96.4%) were males. More than half (58.4%) reported being smokers at the time of their treatment.

The analysis showed varying rates of adherence to quality measures. For instance, negative surgical margins were used in most cases (96.7%), but adequate lymph node sampling was performed in just 1 in 3 cases (34.0%).

Using their scoring system, in which 0 points were awarded in cases where no quality metrics were met and 13 points were awarded when all quality metrics were met, the study investigators found stark differences in patient outcomes.

The median OS was 7.0 years when 12 or 13 quality metric points were earned, but just 2.6 years when 0 to 5 points were earned. A risk-adjusted HR calculation showed the adjusted HR for recurrence-free survival from 12 to 13 points and 0 to 5 points was 0.39 (95% CI, 0.31-0.49).

The investigators then used a data set of more than 107,000 nonveteran patients from the National Cancer Database (NCDB) and found a similar benefit to using quality metrics. They noted that although the VHA is often perceived as providing lower-quality care, its rates of quality-metric adherence were similar to those in the NCDB, despite having higher rates of comorbidities than the general population. They said these data show the VHA is already performing well.

“Nonetheless, both the VHA and NCDB data sets suggest that [quality metric] adherence is variable, presenting an opportunity for significant quality improvement efforts in both practice settings,” they wrote.
Although adherence to quality metrics has improved, the authors said further policy efforts are needed to ensure the metrics become more fully ingrained in everyday practice. 

Reference
Heiden BT, Eaton DB Jr, Chang SH, et al. Association between surgical quality metric adherence and overall survival among US veterans with early-stage non-small cell lung cancer. JAMA Surg. Published online January 18, 2023. doi:10.1001/jamasurg.2022.6826

Study Characterizes Real-world Use of Relugolix in Combination With Other Prostate Cancer Therapies

Relugolix was frequently used in combination with other medications for prostate cancer (PC) in patients both new to androgen deprivation therapy (ADT) and continuing ADT in a real-world study. The results were presented during a poster session at the 2023 American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) in San Francisco, California.¹

Relugolix (Orgovyx) is an oral gonadotropin-releasing hormone (GnRH) receptor antagonist approved in 2020 by the FDA for the treatment of advanced PC based on data from the phase 3 HERO trial (NCT03085095).²

The randomized, open-label study included men who required at least 1 year of ADT, either after recurrence following PC treatment or for newly diagnosed castration-sensitive advanced PC.

A subgroup analysis of HERO found that relugolix in combination with enzalutamide or docetaxel was similarly effective to other study subgroups, the authors noted, but some guidelines do not recommend using relugolix concurrently with other therapies due to limited data.

The new study evaluated real-world use patterns of relugolix and leuprolide, another GnRH agonist, in combination with other PC medications at 89 urology practices across the United States. The observational retrospective analysis examined electronic medical record data for 51,735 patients treated with ADT in 2021. Patients who received either relugolix or leuprolide during the study period were eligible for the analysis, which focused on ADT prescription occurrence and ADT in combination with other medications for PC.

A total of 3096 (6%) patients received at least 1 prescription for relugolix, and 45,599 (88.1%) received leuprolide. The proportion of patients given combination PC regimens was higher among those treated with relugolix vs those treated with leuprolide (22.5% and 19.5%, respectively; P < .0001).

Among patients who were being treated with ADT for the first time in the study, those receiving relugolix were more likely to be on a combination of PC medications compared with leuprolide users (15.8% vs 10.9%, respectively). In both the relugolix and leuprolide groups, the most common medications used concurrently were novel antiandrogen therapies.

The therapies most frequently combined with relugolix were enzalutamide, apalutamide, abiraterone, and darolutamide (9%, 6.9%, 5.9%, and 1.1%, respectively). In the leuprolide cohort, the same PC medications were seen at similar proportions.

Overall, the study suggests that in the real world, relugolix is frequently combined with other PC medications among patients both new to and continuing ADT. In the relugolix cohort, the proportion of patients undergoing combination therapy was also higher than the proportion of patients receiving combination therapy with leuprolide.

“These results provide insight into the real-world use of relugolix in combination with other PC medications,” the authors concluded. “Further analyses are needed to make informed treatment decisions.” 

References
1. McKay RR, Gandhi R, Yang E, Pruett J, Nwokeji E, Fallick M. Real-world combination therapy patterns in patients receiving leuprolide or relugolix for androgen deprivation therapy in 2021 (The REAL-ADT COMBO study): analysis from a US EMR database. Abstract presented at: 2023 ASCO GU Cancers Symposium; February 16-18, 2023; San Francisco, CA. Accessed February 17, 2023. https://meetings.asco.org/abstracts-presentations/216934
2. FDA approves relugolix for advanced prostate cancer. FDA. December 18, 2020. Accessed February 17, 2023. https://www.fda.gov/drugs/resources-information-approved-drugs/fda-approves-relugolix-advanced-prostate-cancer