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At 7 years, adjuvant abemaciclib (Verzenio; Eli Lilly) plus endocrine therapy (ET) resulted in statistically significant and clinically meaningful improvement in overall survival (OS) in patients with hormone receptor-positive (HR+)/HER2-negative (HER2–), node-positive, high-risk early breast cancer (eBC). The data, from the monarchE trial (NCT03155997), were presented at the European Society of Medical Oncology 2025 Congress.¹

HR+/HER2– metastatic breast cancer (mBC) represents the most prevalent subtype, comprising approximately 72.7% of all breast cancer cases. Managing this population remains challenging, as tumors with HER2 alterations often exhibit aggressive behavior, underscoring the urgent need for more effective treatment options.²

Abemaciclib, a CDK4/6 inhibitor, has received multiple FDA approvals for use in combination with ET or aromatase inhibitors across various settings. The drug was first approved in 2017 as a monotherapy for adults with HR-positive, HER2-negative advanced or metastatic breast cancer whose disease had progressed following prior endocrine therapy. Since then, its indications have expanded as follows³:

• 2018: Approved in combination with an aromatase inhibitor as initial endocrine-based therapy for postmenopausal women with HR+/HER2– advanced or metastatic breast cancer.
• 2021: Approved in combination with ET (tamoxifen or an aromatase inhibitor) for the adjuvant treatment of adults with HR+/HER2–, node-positive, early breast cancer at high risk of recurrence.
• 2023: Indication expanded for use with ET in adults with HR+/HER2–, node-positive, early breast cancer at high risk of recurrence.

The phase 3 monarchEtrial was an open-label, randomized study evaluating adjuvant abemaciclib in combination with ET for patients with high-risk, HR+/HER2– eBC. Participants were assigned in a 1:1 ratio to receive ET for at least 5 years, with or without abemaciclib for the first 2 years.⁴

High-risk disease was defined as having either 4 or greater positive axillary lymph nodes (ALN) or 1 to 3 ALN with grade 3 disease and/or tumor size greater than or equal to 5 cm (Cohort 1). Patients with 1 to 3 ALN and centrally confirmed Ki-67 greater than or equal to 20% were included in Cohort 2. The intent-to-treat (ITT) population included both cohorts (n = 5637).⁴

“[The trial] enrolled high-risk patients—those with either 4 or more positive lymph nodes, or 1 to 3 nodes with grade 3 disease or a large tumor size. An additional cohort included patients with lower clinicopathologic risk features, but a high Ki-67 index,” Stephen R. D. Johnston, MA, FRCP, PhD, professor of Breast Cancer Medicine Breast Unit Department of Medicine Royal Marsden Hospital London, said. “Following local and regional therapy, and chemotherapy in approximately 95% of these high-risk patients, participants were randomized to receive either endocrine therapy alone or endocrine therapy plus two years of abemaciclib.”

The primary end point, EFS, was assessed with OS designated as a key secondary end point. Because the type 1 error was not controlled, OS was evaluated using a gated testing strategy after the primary invasive disease-free survival analysis. Following discussions with regulators, the target number of events was increased from 390 to 650 to allow a minimum follow-up of 5 years and to generate a more mature and robust survival dataset.⁴

After a median follow-up of 6.3 years, 301 deaths occurred in the abemaciclib plus ET arm compared with 360 in the ET-alone arm. The addition of abemaciclib reduced the risk of death by 15.8%(HR, 0.84; 95% CI, 0.72–0.98; P = .027), achieving statistical significance.⁴

OS improvement was observed across all predefined subgroups. Durable benefits in IDFS and distant relapse–free survival (DRFS) was maintained through 7 years, with hazard ratios of 0.73 (95% CI, 0.66–0.82) and 0.75 (95% CI, 0.66–0.84), respectively.⁴

At 7 years, IDFS rates were 77.4% with abemaciclib plus ET vs 70.9% with ET alone, while DRFS rates were 80.0%vs74.9%, representing absolute gains of 6.5% and 5.1%. More patients in the ET-only arm (52%) went on to receive CDK4/6 inhibitors in the metastatic setting than in the abemaciclib plus ET arm (34%). In cohort 1, results for IDFS, DRFS, and OS were consistent with the ITT findings. Long-term safety data showed no new or delayed toxicities.⁴

Two years of adjuvant abemaciclib combined with ET produced a statistically significant and clinically meaningful OS advantage compared with ET alone in patients with HR+/HER2–, node-positive, high-risk eBC. Sustained improvements in IDFS and DRFS were maintained through 7 years, reinforcing the long-term benefit of this treatment approach.⁴

“The addition of abemaciclib results in a 1% difference in 5 years, 1.3% in 6 years, 1.8% at 7 years,” said Stephen R. D. Johnston, MA, FRCP, PhD, professor of Breast Cancer Medicine Breast Unit Department of Medicine Royal Marsden Hospital London, “so with a median follow up of 6.3 years, abemaciclib has reduced the risk of death by 15.8% compared to endocrine therapy alone.”

These findings highlight the sustained efficacy of adjuvant abemaciclib when added to endocrine therapy, demonstrating not only improved survival outcomes but also a meaningful reduction in disease recurrence and progression to metastatic breast cancer. By lowering the number of patients who develop metastatic disease, the therapy may further enhance long-term overall survival, reinforcing its role as a critical treatment option for patients with high-risk HR+/HER2– early breast cancer.

“In conclusion, the primary OS analysis demonstrates that 2 years of abemaciclib combined with [ET] resulted in a statistically significant improvement in [OS] in the ITT population, reducing the risk of death by 15.8%,” explained Johnston. “Importantly, this translates into a clinically meaningful impact, with fewer patients developing metastatic disease—approximately 30% fewer—an effect that is expected to contribute to an even greater overall survival benefit over time.”

REFERENCES

1. Endocrine therapy with or without abemaciclib (LY2835219) following surgery in participants with breast cancer (monarchE). Updated April 20, 2025. Accessed August 28, 2025. https://clinicaltrials.gov/study/NCT03155997

2. Gerlach A. Patritumab deruxtecan meets primary end point in ICARUS-BREAST01 trial. Pharmacy Times. September 9, 2025. Accessed October 17, 2025. https://www.pharmacytimes.com/view/patritumab-deruxtecan-meets-primary-end-point-in-icarus-breast01-trial

3. Gerlach A. Abemaciclib plus endocrine therapy improves survival in patients with HR+/HER2– breast cancer. Pharmacy Times. August 28, 2025. Accessed October 17, 2025. https://www.pharmacytimes.com/view/abemaciclib-plus-endocrine-therapy-improves-survival-in-patients-with-hr-her2-breast-cancer

4. Johnston S, Martin M, O’Shaughnessy J, et al. LBA13 – monarchE: Primary overall survival (OS) results of adjuvant abemaciclib + endocrine therapy (ET) for HR+, HER2-, high-risk early breast cancer (EBC). Presented at: European Society of Medical Oncology 2025 Congress. October 17, 2025, to October 21, 2025. Abstract LBA13

Story Continues

Regorafenib (Stivarga) plus nivolumab (Opdivo) displayed noninferior survival and a numerically higher response rate and disease control rate (DCR) compared with chemotherapy for patients with previously treated, refractory, advanced gastric or gastroesophageal junction (GEJ) cancer, according to findings from the phase 3 INTEGRATE IIb (NCT04879368) presented at the European Society for Medical Oncology (ESMO) Congress 2025.

Among patients in the intent-to-treatment population in the regorafenib arm (n = 309) vs the chemotherapy arm (n = 153), the median overall survival (OS) was 5.9 months vs 6.3 months (HR, 0.88; 95% CI, 0.71-1.09; P = .23). Additionally, the median progression-free survival (PFS) in the respective arms was 1.9 months (95% CI, 1.8-2.0) vs 1.9 months (95% CI, 1.8-2.0; HR, 0.85; 95% CI, 0.69-1.05).

Furthermore, a numerically higher objective response rate (ORR) was observed among patients treated with regorafenib plus nivolumab vs chemotherapy, with respective rates of 7.4% vs 2.6% (OR, 2.99; 95% CI, 1.00-12.11). The DCR in the regorafenib and chemotherapy arms was 39% vs 26% (OR, 1.84; 95% CI, 1.18-2.90), with 12-month DCR rates of 14% (95% CI, 8.5%-21%) vs 0% (95% CI, not estimable [NE]), respectively.

Global quality of life (QOL) was numerically improved with regorafenib, with 12-month deterioration-free rates of 3.9% (95% CI, 2.1%-6.5%) vs 0.7% (95% CI, <0.1%-3.5%) with chemotherapy (HR, 0.74; 95% CI, 0.60-0.91). Additionally, the physical functioning QOL scores exhibited similar values, with event-free rates of 3.9% (95% CI, 2.1%-6.5%) and 0.7% (95% CI, <0.1%-3.5%), respectively (HR, 0.86; 95% CI, 0.70-1.05).

“[Regorafenib plus nivolumab] was not superior to investigator’s choice of chemotherapy in third- or later-line treatment,” presenting investigator, David Goldstein, MBBS, FRACP, PRCP, conjoint clinical professor and senior staff specialist in the Department of Medical Oncology at Prince of Wales Hospital in Syndey, Australia, stated in the presentation. “We note that secondary end points of ORR and DCR were numerically higher in the [experimental] arm, without any adverse impact on global QOL and a prolonged 12-month time to deterioration in the regorafenib/nivolumab arm.”

In the phase 3 AGITG intergroup study, patients with unresectable locally advanced, metastatic, or recurrent gastric or GEJ adenocarcinoma who previously received at least 2 prior lines of chemotherapy—including a platinum-containing agent and fluoropyrimidine —were randomly assigned 2:1 to receive the regorafenib/nivolumab regimen or chemotherapy. Those eligible for enrollment also must have had an ECOG performance status of 0 or 1, and those with HER2-positive disease must have received trastuzumab (Herceptin).

Treatment in the investigational arm consisted of 90 mg of daily oral regorafenib on days 1 to 21 of each 28-day cycle and intravenous nivolumab at 240 mg on day 1 of each 14-day cycle for 2 months of treatment, followed by 480 mg of intravenous nivolumab on day 1 of 28-day cycles. The chemotherapy regimen used was determined by the investigator’s choice and consisted of taxane-based chemotherapy (25%), irinotecan (25%), or trifluridine/tipiracil (Lonsurf; 49%). In both arms, treatment continued in the absence of disease progression or unacceptable toxicity.

In the investigational and control arms, 48% in each arm were treated in Asia, 73% vs 75% were male, and the median age was 63 years (range, 22-85) vs 63 years (range, 24-83). Most patients were previously treated with VEGF inhibitors (61% vs 59%), had an ECOG performance status of 1 (57% vs 55%), and had gastric disease (63% vs 59%). A total of 33% vs 33% received prior immunotherapy, 44% vs 44% received more than 2 prior lines of therapy, and 50% vs 48% had more than 2 metastatic sites of disease.

The primary end point of the study was OS. Secondary end points included PFS, ORR, DCR, QOL, and safety.

Any-grade adverse effects (AEs) were observed in 98% of the regorafenib/nivolumab arm vs 92% of the chemotherapy arm; 58% vs 38%, 8% vs 10%, and 4% vs 1% experienced grade 3, 4, and 5 AEs, respectively. The frequency of serious AEs (SAEs) in either arm was 41% vs 25%. However, Goldstein noted that an expedited reporting for SAEs was not required in the chemotherapy arm, and an imbalance in the reporting of these events was expected.

The most common grade 3 or higher AEs in the investigational and control arms included neutrophil count decreases (3% vs 18%), anemia (6% vs 9%), fatigue (6% vs 4%), nausea (1% vs 7%), aspartate aminotransferase increases (5% vs 3%), and platelet count decreases (6% vs 2%).

Reference

Goldstein D, Sjoquist K, Espinosa D, et al. Regorafenib plus nivolumab vs investigator’s choice of chemotherapy in previously treated gastric or gastroesophageal cancer: INTEGRATE IIb, a randomized phase 3 AGITG Intergroup [NHMRC-CTC/IKF/AIO, ACCRU, TCOG/NHRI] study. Presented at the European Society for Medical Oncology (ESMO) Congress 2025; October 17-21, 2025; Berlin, Germany. Abstract LBA80.

When it comes to nutrition trends, protein is having a major moment. Walk down the aisle of any grocery store and you can find protein-infused popcorn, yogurt, ice cream and more. And, of course, there are plenty of protein powders and shakes to buy. If you rely on the latter to get more protein into your diet, you’ll want to pay attention: Recently, Consumer Reports launched an investigation to look into what those powders and shakes actually contain. The results: Of the 23 brands it tested, more than two-thirds contained more lead than food safety experts say is safe to consume in one day.

Before rushing to throw out all the protein products currently in your pantry, read on to learn more about what this news really means — including how concerned you need to be.

Is there lead in protein powders and shakes?

Consumer Reports tested 23 protein powders and ready-to-drink shakes. Through this testing, it was found that approximately two-thirds of those tested contain more lead in a single serving than experts say is safe, which is under 0.5 micrograms a day. Some even had up to 10 times the recommended daily intake, according to the report.

Of all of the protein powders and shakes tested, plant-based options had, on average, much higher levels of lead than those that were dairy or animal-based. The dairy-based protein products had the lowest amount of lead, but several still had high enough numbers that experts from Consumer Reports advised against using them daily. NBC Select has not independently verified these findings.

Why is consuming high levels of lead potentially dangerous?

According to the World Health Organization (WHO), consuming high levels of lead can impact your body in various ways and is considered to be harmful. Once lead is consumed, it is distributed to various organs — including the brain, kidneys and bones. High levels of lead exposure have been connected to anaemia, hypertension, renal impairment, cardiovascular issues and more, according to WHO.

Which brands had high levels of lead?

As mentioned, Consumer Reports tested 23 protein powders and ready-to-drink shakes. Based on the results, it sorted the tested items into three categories: what you should avoid, what you should limit and what its experts deemed safe to consume. NBC Select has not independently verified these findings.

Those results can be found below:

Products to avoid

• Naked Nutrition Vegan Mass Gainer
• Huel Black Edition

Suggested to limit to once a week

• Garden of Life Sport Organic Plant-Based Protein
• Momentous 100% Plant Protein (no longer available)

Okay for occasional use

How protein companies are responding to this new report

We reached out to all 23 of the manufacturers with protein powders and shakes that were deemed not safe for daily consumption by Consumer Reports. At the time of publication, six companies responded to our request for comment.

Here’s what they said:

Garden of Life: “At Garden of Life, we carefully select ingredients to meet our high standards for quality and safety in order to ensure that our products are safe. Certain substances, such as heavy metals, commonly occur in the environment in soil and water. This may result in low levels of heavy metals in agricultural raw materials. Garden of Life products are tested for heavy metals, and the levels are below established food safety thresholds.

All of our products are safe to consume and consistently adhere to our own and established government standards and food safety guidance. We can assure that our products are safe for daily use because we apply this food safety guidance as our product release criteria.”

Huel: “We are extremely disappointed by this report, which the NPA described here as ‘alarmist, misleading and unscientific’ and the CRN have described here as creating a ‘misleading impression of risk.’ We have responded in this article in full.

Trace minerals such as lead occur naturally in our planet and so are found in soil, water and plants. For context, a meal of sausages, potatoes, cabbage and carrots can contain around 5 micrograms (µg) of lead, and most adults consume between 20 and 80 micrograms (µg) per day from normal foods. Huel is no different from everyday meals in this respect.

The Consumer Reports article is based on California’s Proposition 65, which uses an ultra conservative threshold of 0.5 micrograms (µg) of lead per day. California rules divide the observable effect limit by 1000 to allow a margin for error. For comparison, the EU benchmark is 270 micrograms (µg) per serve.

It is important to understand that the Consumer Reports approach reflects a uniquely cautious regulation rather than an internationally accepted measure of consumer safety.

Over the past three years, we have carried out 17 independent tests on Huel Black Edition powder alone, with results consistently showing lead levels between 1.5 and 2.2 micrograms (µg) per 90 g serving. These results are well within all recognised safety limits. Huel has also recently been accredited by NSF, the gold standard for product safety and quality, and the most recent NSF report showed undetectable levels of lead (‘non-detectable’ at their 3.6 microgram (µg) tolerance). It is important to note that we are talking about miniscule variations here of 2 millionths of a gram versus 6 millionths of a gram.”

Kos: “Please note that all KOS products are third-party tested in accordance with USDA Organic and FDA standards…Traces of metal and lead are found within the natural environment, and we do our best to filter them out as much as possible.”

Momentous: You can find a full statement from the brand here. A spokesperson for the brand also told us: “[The] Momentous products tested have been discontinued and are no longer commercially available. Momentous began selling its latest formulation for both Whey and Plant proteins earlier this year, with v1 products (used for the report) being fully sunsetted in all channels by March 2025.”

Orgain: “At Orgain, we carefully select ingredients to meet our high standards for quality and safety in order to ensure that our products are safe. Certain substances, such as heavy metals, commonly occur in the environment in soil and water. This may result in trace amounts being present in agricultural ingredients — such as plants, grains and other raw materials — that go into our products. Orgain products are tested for heavy metals, and the levels are below established food safety thresholds. 

Our products are safe to consume and consistently adhere to our own and established government standards and food safety guidance. We can assure that our products are safe for daily use because we apply this food safety guidance as our product release criteria.”

Optimum Nutrition: “We share Consumer Reports’ commitment to consumer safety. All our Optimum Nutrition and BSN products are made in compliance with the FDA’s Good Manufacturing Practices, and we hold ourselves to even higher standards.

We test for heavy metals in the raw materials we use, formulate products so they are compliant with California Prop 65 criteria (among the strictest in the world), and test finished products through accredited third-party labs.

The health and safety of our consumers is our top priority. We’re pleased to see that Consumer Reports recommends our Optimum Nutrition Gold Standard Whey and BSN Syntha-6 as ‘better choices for daily consumption’.”

Other protein powders and shakes from Consumer Reports’ testing

Through its testing, Consumer Reports identified the below seven protein powders and shakes that contain low enough levels of lead for experts to consider them safe for daily consumption.

This chocolate ready-to-drink shake is plant-based and contains 32 grams of protein in one bottle, according to the brand. The formula is sugar-free and contains 9 amino acids., which can help with energy, according to Owyn. I’ve had this drink on a handful of occasions and find it to have a pleasantly sweet chocolate taste. The consistency is on the thicker side, so if that bothers you, you may want to skip.

This protein powder is intended for those trying to gain muscle. It has 53 grams of grass-fed protein, 110 grams of carbs and 15 grams of health fats, according to the brand. It also contains creatine, which can help with muscle gain and post-workout recovery, according to Transparent Labs.

Made from whey, this protein powder has 24 grams of protein for 120 calories per serving. You can use it before a workout, as a meal replacement or in between meals. Reviewers like the rich chocolate flavor and find that it dissolves easily in liquid.

This powder is made from whey and has 24 grams of protein and two grams of sugar in a single serving. Reviewers note that the cookies and cream flavor tastes like a milkshake. You can drink it by simply mixing it with water or milk or mix it into a smoothie or oatmeal.

The protein in this powder is sourced from grass-fed European dairy cows, according to the brand. It has 20 grams of protein per serving and is free from soy. A 1.4-pound tub has 25 servings and you can choose from vanilla, strawberry, chocolate or unflavored.

Another option for those looking to pack on muscle, this powder is calorie-dense and has 52 grams of protein in a single serving. It also has creatine to support muscle growth and vitamins A, C and E for overall health, according to the brand.

Why trust NBC Select?

Bethany Heitman is a weekend editor at NBC Select and a journalist who regularly reports on recall alerts — including recalls surrounding air conditioners and hand soap. She also commonly covers common questions pertaining to health and wellness — like whether plastic baby bottles are safe.

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