Kristie L. Kahl is vice president of content at MJH Life Sciences, overseeing CURE®, CancerNetwork®, the journal ONCOLOGY, Targeted Oncology, and Urology Times®. She has been with the company since November 2017.

She is a graduate of Rider University, where she acquired a Bachelors of Art in journalism, as well as a graduate of Temple University, where she received her Masters of Science in Sports Management.

Follow Kristie on Twitter at @KristieLKahl, or email her at kkahl@mjhlifesciences.com.

Kristie L. Kahl

Dr. Mabel Mardones educates patients on breast cancer updates: © stock.adobe.com.

It is crucial to understand the characteristics of the disease following a diagnosis of metastatic breast cancer, especially the cancers subtypes and associated biomarkers, as these directly impact the direction of treatment decisions. Moreover, advancements in treatment strategies within the therapeutic landscape aims to manage disease, control progression, as well as maintain quality of life for patients.

At a CURE® Educated Patient® Metastatic Breast Cancer Updates event, which was held in tandem with Rocky Mountain Cancer Centers, Dr. Mabel Mardones led a variety of discussions around understanding metastatic breast cancer and its subtypes. Notably, she focused on estrogen receptor (ER)-positive, human epidermal growth factor receptor 2 (HER2)-negative breast cancer.

“[One takeaway is] just understanding a lay of the land as to how a medical oncologist thinks and some updates in ER-positive metastatic disease, such as learning about staging and [circulating tumor cells], minimal residual disease scans, targeted options, [and more],” she explained.

Mardones is a board-certified medical oncologist and hematologist with a sub-specialty of expertise in breast cancer.

Breast cancer is a heterogeneous disease, meaning it presents with diverse characteristics among different patients.

The primary subtypes of breast cancer are defined by the presence or absence of specific receptors on the surface of the cancer cells, including:

Hormone receptor (HR)-positive breast cancer: This includes ER-positive and/or progesterone receptor (PR)-positive breast cancer. These cancers are fueled by the hormone’s estrogen and/or progesterone.

HER2-positive breast cancer: These cancers have an overexpression of the human epidermal growth factor receptor 2 protein, which promotes cell growth.

Triple-negative breast cancer (TNBC): These cancers lack expression of estrogen receptors, progesterone receptors and HER2.

To determine one’s subtype of disease, biomarker testing provides specific information about the characteristics of a patient’s tumor. Further, biomarker testing can indicate whether a specific treatment, such as hormone therapy or targeted therapy, is likely to be effective. For example, the presence of specific gene mutations, such as PIK3CA or ESR1 mutations, can also guide the selection of targeted therapies.

Treatment Options for ER-Positive, HER2-Negative Disease

For patients with ER-positive, HER2-negative metastatic, hormone therapy – which blocks the effects of estrogen, thereby inhibiting the growth of cancer cells that rely on estrogen for proliferation – is typically the initial systemic treatment approach. These typically include aromatase inhibitors and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors.

In addition, for premenopausal women, ovarian suppression (which stops the ovaries from producing estrogen) or ovarian ablation (permanent removal of ovarian function) may be used in conjunction with hormone therapy.

If cancer progresses or treatment stops working, the next lines of therapy are considered based on the patient's prior treatments, the presence of new mutations and the overall disease characteristics.

Options in the second-line setting and beyond can include selective estrogen receptor degraders (SERDs), PI3K inhibitors, AKT inhibitors

“There's lots of options in the combination [therapy] space, in the first and second line with oral SERDs and CDKs. There's lots more options for targeted therapies and the PIK3CA space; there's at least four or five other agents and trials that are coming up in that space,” Mardones stated. “[Those agents] came up in the conversation at our meeting too, about their toxicities, which are, unfortunately quite a lot. Although effective agents, they are not conducive to really great quality of life for a long time.”

She concluded her discussion at the CURE® Educated Patient® Metastatic Breast Cancer Updates event by highlighting the need for more oral treatment options for patients.

For more news on cancer updates, research and education,

don’t forget to subscribe to CURE®’s newsletters here.

Articles

Understanding metastatic breast cancer subtypes and associated biomarkers is essential for guiding treatment decisions. Advancements in treatment strategies aim to manage disease progression and maintain patient quality of life. Dr. Mabel Mardones emphasized the importance of understanding ER-positive, HER2-negative breast cancer, discussing staging, circulating tumor cells, and targeted options. Biomarker testing helps determine effective treatments, such as hormone or targeted therapies. For ER-positive, HER2-negative metastatic breast cancer, hormone therapy is the initial approach, with additional options like SERDs and PI3K inhibitors available if cancer progresses.

Dr. Mabel Mardones educates patients on breast cancer subtypes, as well as treatment options for those with ER-positive, HER2-negative disease.

Understanding Breast Cancer Biomarkers Drives Patient Treatment Decisions

The ADC zilovertamab vedotin plus Rituxan and chemo showed an ORR of 56.3% in relapsed/refractory DLBCL: © stock.adobe.com. 

Among patients with with relapsed or refractory diffuse large B-cell lymphoma (DLBCL), zilovertamab vedotin, a ROR1-targeted antibody-drug conjugate, plus Rituxan (rituximab) and gemcitabine-oxaliplatin (R-GemOx) elicited an objective response rate of 56.3%, according to findings from the phase 2/3 waveLINE-003 study which were shared at the 

At the recommend phase 2 dose of 1.75 milligrams per kilogram (mg/kg) for zilovertamab vedotin plus standard R-GemOx, the complete response rate was 50% in the study. After a median of 9.9 months of follow-up, the median duration of response was 8.7 months, with 28.6% of patients continuing to respond at nine months. The median overall survival was not yet reached, with a 12-month estimated overall survival rate of 68.9% at the RP2D.

"This combination had a manageable safety profile, and the objective and complete response rate of 56% and 50% of the zilovertamab vedotin plus R-GemOx combination at the recommended phase 2 dose suggest improved activity in relapsed/refractory DLBCL," said principal investigator Dr. Philippe Armand, from Dana-Farber Cancer Institute. "The study is currently enrolling the phase 3 portion."

The phase 2 portion of the study enrolled 40 participants with relapsed/refractory DLBCL. R-GemOx was administered at standard doses in each group, with zilovertamab escalated across three dose levels. There were 17 patients who received 1.5 mg/kg, 16 receiving 1.75 mg/kg, and seven who received 2.0 mg/kg. Across all groups, the median number of prior therapies was two, with two specifically having received the CD79b-directed Polivy (polatuzumab vedotin). Armand noted this agent specifically, as it carries the same cytotoxic payload as zilovertamab vedotin; however, data were not shown for this subgroup during the presentation.

Across all patients enrolled, the median age was 66.5 years, with 55% being 65 years or older. ECOG performance status was zero (43%), one (48%), and two (10%) and nearly half of patients had Ann Arbor stage IV disease (53%). The DLBCL cell of origin was most commonly GCB (45%).

At the 1.5 mg/kg dose, the overall response rate was 26.7% with a complete response rate of 20.0%. The median duration of response in this group was 14.4 months, with a 9-month duration of response rate of 100%. The median overall survival was 11.5 months in this group, with a 12-month overall survival rate of 40.8%. The median follow-up for this dose level was 18.1 months.

In the 2.0 mg/kg group, the overall response rate was 57.1%, with a complete response rate of 42.9%. The median duration of response in this group was not yet reached. The median overall survival in this group was 7.4 months, with a 12-month overall survival rate that was not yet reached. The median follow-up in this cohort was 9.3 months.

"The obvious caveat here are the few patients and still limited duration of follow up. So, the estimates are not very stable," Armand cautioned regarding the response duration data.

There was a total of 7 dose limiting toxicities observed across the three dose levels. At the 2.0-mg/kg dose, there were four, compared with one in the 1.5-mg/kg group and two at the recommended phase 2 dose group. In the 2.0-mg/kg dose level, there was one treatment-related death from sepsis.

Other dose limiting toxicities in this group included grade 3 diarrhea, grade 4 neutrophil count decrease, grade 4 thrombocytopenia, grade 3 febrile neutropenia, and grade 4 neutrophil count decrease. To address these side effects, midway through the trial the protocol was adapted to included mandatory prophylaxis with G-CSF. In the recommended phase 2 dose arm, the dose limiting toxicities were grade 3 alanine aminotransferase increase and intestinal obstruction.

This combination had a manageable safety profile, and the objective and complete response rate of 56% and 50% of the zilovertamab vedotin plus R-GemOx combination at the recommended phase 2 dose suggest improved activity in relapsed/refractory DLBCL.

Zilovertamab vedotin-related side effects of grade 3 (severe)/4 (life threatening) in severity were experienced by 63% of patients in the recommended phase 2 dose group. This compared with 86% of those in the largest dose and for 53% of those in the lowest dose. Two patients discontinued the drug in the highest dose group, related to sepsis and respiratory fatigue. There were no discontinuations at the other dose levels. Serious drug-related side effects were experienced by 24% of those in the low dose group, by 31% at the recommended phase 2 dose group, and for 57% of those at the 2.0 mg/kg dose.

Several studies continue to explore zilovertamab vedotin for patients with DLBCL, including the phase 3 portion of the waveLINE-003 study. Armand also drew attention to studies looking at zilovertamab vedotin as a first-line treatment for DLBCL in combination with chemotherapy compared with chemo alone. Additionally, waveLINE-011 is investigating zilovertamab vedotin with chemo as a first-line therapy for the GCB subtype of DLBCL compared with Polivy plus chemo.

“WaveLINE-003: Phase 2/3 trial of zilovertamab vedotin plus standard of care in relapsed/refractory diffuse large B-cell lymphoma” by Dr. Philippe Armand, et al., American Society of Clinical Oncology Annual Meeting.

Zilovertamab vedotin, a ROR1-targeted antibody-drug conjugate, combined with Rituxan and gemcitabine-oxaliplatin, demonstrated a 56.3% objective response rate in relapsed/refractory diffuse large B-cell lymphoma (DLBCL) patients. At the recommended phase 2 dose of 1.75 mg/kg, the complete response rate was 50%, with a median response duration of 8.7 months. The safety profile was manageable, though severe side effects were noted. The study is progressing to phase 3, with ongoing investigations into zilovertamab vedotin as a first-line treatment for DLBCL.

The antibody-drug conjugate zilovertamab vedotin plus Rituxan and chemotherapy showed an objective response rate of 56.3% in relapsed/refractory DLBCL.

Zilovertamab Vedotin Plus Chemo Combo Shows Responses in R/R DLBCL 

Dr. Alicia Morgans discussed complications associated with androgen deprivation therapy in prostate cancer: © stock.adobe.com.

Androgen deprivation therapy (ADT), often referred to as hormonal therapy, is effective in slowing cancer growth among men with prostate cancer; however, maintaining quality of life in tandem with its side effects is important.

ADT works by significantly lowering testosterone levels, a hormone vital for prostate cancer cell growth. “It is essentially the food or the fuel that drives those cells to do the things that they want to do, which in this case, is something we don't want them to do: to replicate or to grow,” explained Dr. Alicia Morgans. However, she added that this intentional reduction can lead to a range of side effects impacting overall well-being among patients with prostate cancer.

At the CURE Educated Patient Prostate Cancer Summit, Morgans, a genitourinary medical oncologist and the director of the Survivorship Program at Dana-Farber Cancer Institute, shed light on these potential complications and offered strategies to maintain a high quality of life during and after treatment with ADT.

Morgans explained that ADTs work by disrupting the body's natural testosterone production by targeting the pituitary gland in the brain, which normally stimulates the testes to produce testosterone.

“These drugs that we use are (gonadotropin-releasing hormone, or GnRH) agonists or antagonists ¾ GnRH being a receptor that's on the pituitary gland that normally is stimulated by other parts of the brain and the hypothalamus to cause this testosterone production, but when we act on those receptors with these medicines, we cause all kinds of feedback loops that ultimately cause the testes to stop producing testosterone, and that testosterone level goes down very, very low,” she said.

However, in addition to reductions in testosterone levels, a secondary effect of ADT occurs on men’s estrogen levels. “These estrogen levels are lower than that that we see in postmenopausal women, and that combination of low hormone levels is what explains a lot of the symptom burden that we see when we use androgen deprivation therapy and see the complications that we do,” Morgans added.

The impact of ADT extends to various bodily systems; therefore, patients need to understand these potential medical complications to manage them effectively with their care teams.

Because heart disease is a leading cause of death in the US, patients should be aware of their risk for cardiovascular disease, regardless of cancer status, according to Morgans. “This heart risk and cancer risk of mortality are competing throughout somebody's life. So it's really important that we emphasize an interest in and an understanding of heart disease and ways that we can reduce the risk of complications from heart disease.”

In regard to treatment with ADTs, low testosterone levels may contribute to factors that increase cardiovascular risk, such as increased total cholesterol, increased triglycerides, increased abdominal adipose tissue, impaired glucose metabolism or weight gain.

Particularly, one study evaluated 100 consecutive patients with prostate cancer who were going to a urology clinic. The common coronary artery disease risk factors seen were hypertension (58%), dyslipidemia (high cholesterol; 51%) and diabetes (17%). Further, 17% reported coronary artery disease, of which nine had a history of stents and five had bypass surgery on their heart.

Out of 100 patients, only four had no cardiac risk factors. “Most people are going to have some risk factors, and we need to do something to prevent progression of those risk factors into disease,” Morgans said, adding that a history of heart disease increases the risk of heart complications in patients being treated with ADT.

In addition to cardiovascular risk, treatment with ADT is also associated with insulin resistance.

In a retrospective cohort study, researchers found that patients with prostate cancer demonstrated a 36% higher risk of being diagnosed with diabetes 12 months after initiating treatment with ADT (1,231 patients), compared with patients who had not received this type of treatment (7,250 patients). Morgans explained that this is because treatment with ADT can lead to insulin resistance, meaning a patient’s body needs more insulin to keep blood sugar levels stable.

In addition, Low testosterone and low estrogen levels due to treatment with ADT can negatively impact bone density. Morgans explained that bones are constantly undergoing a process of remodeling, with old bone being reabsorbed and new bone being formed. Therefore, during treatment with ADT, bone breakdown outpaces formation, leading to a loss of bone density, in turn, increasing the risk of osteoporosis (thin, brittle bones) and fractures.

“And if we do see someone who develops a fracture, particularly a hip fracture, this can cause loss of mobility, loss of independence and has financial implications when people can't work and can't take care of themselves, so we absolutely try to prevent this and make sure that it's not a problem for people,” she said.

Morgans highlighted guidelines and a systemic approach to the A, B, C, D, Es of being proactive about some of these complications, which included:

wareness: Patients should be informed about the potential cardiovascular risks associated with ADT.

lood Pressure: Patients should regularly monitor and manage blood pressure.

igarettes: Patients should monitor and manage cholesterol levels, and if they smoke, quitting is paramount.

iabetes: Patients should adopt a heart-healthy diet, such as the Mediterranean diet, which is low in saturated fats and red meat, and focus on weight management. If a patient has diabetes, they should diligently manage their blood sugar.

xercise: Patients should engage in regular physical activity.

Further, to address issues with bone density, Morgans recommended that patients take 1,000 to 1,200 milligrams of calcium and 400 to 1,000 units of vitamin D daily, participate in weight-bearing exercises like walking, and talk to their doctors if there would be benefit from medications that help strengthen bones.

Depression is a common, yet often underdiagnosed, condition in the general population, and can affect a vast majority of patients with cancer. Morgans discussed a study that showed among more than 78,000 men with prostate cancer, of the 43% being treated with ADT, their risk for depression increased by 23%.

“We … need to think about depression and think about cognitive change and ask about it in clinic visits … (and) screen for things like depression,” she said. “…These general screening tools can be really helpful to identify depression, and we have multiple treatments that we can use to treat depression: medicines, counseling, even support groups can be helpful, and exercise can be helpful here.”

In addition, cognitive complications, such as learning and memory, can arise as a result of low testosterone. Morgans explained that testosterone crosses the blood-brain barrier and acts in learning and memory, having a protective effect in preventing cognitive declines. Therefore, lower levels of testosterone can be associated with poorer visual and verbal memory.

“When it comes to cognitive change, we also rely on these general screening tools, and we sometimes refer people to a geriatrician or to a neurologist for an evaluation,” she said. “We can all work together to make these diagnoses with family members, and we can use primary care doctors, psychologists, psychiatrists to help us treat these disorders as well.”

Sexual dysfunction is a common concern among men with prostate cancer, stemming from various factors including nerve issues from surgery or radiation, psychological distress related to cancer and the loss of libido, or sex drive, and interest in sex caused by treatment with ADT.

“It's really important that, if it is something important to patients or to an individual patient or a couple, that they talk about it with their doctor and think about ways to potentially improve things,” Morgans said, adding that there are medications that can be used, as well as a vacuum erection device or penile prosthesis, as well as other ways of sharing intimacy for counseling services available to aid with sexual dysfunction.

“Patients with prostate cancer who are living with or after hormonal treatment are at risk for multiple challenges, multiple complications, including things that affect heart, bones, muscles, blood sugar, mood and other systems. But there are ways that we can identify these challenges and prevent or reverse the effects,” Morgans concluded. “Through exercise, healthy diet, working with primary care, making the diagnosis is the first step, and talking with loved ones about what you need and what they need can be critical, and again, making life better during or after ADT.”

Androgen deprivation therapy (ADT) is a cornerstone in prostate cancer management, effectively slowing cancer growth by reducing testosterone levels. However, this reduction can lead to significant side effects, including cardiovascular risks, insulin resistance, and bone density loss. Patients undergoing ADT should be proactive in managing these risks through lifestyle modifications and regular monitoring. Additionally, ADT can impact mental health, cognitive function, and sexual health, necessitating comprehensive care strategies. Addressing these challenges involves a multidisciplinary approach, emphasizing exercise, diet, and open communication with healthcare providers and loved ones.

Dr. Alicia Morgans discussed complications associated with ADT in prostate cancer, and how men can still maintain quality of life regardless.

Addressing Complications from ADT Therapy to Treat Prostate Cancer

Dr. Guru Sonpavde discusses the CheckMate 901 trial evaluating Opdivo plus Yervoy for those with cisplatin-ineligible, metastatic urothelial carcinoma

Breaking Down the CheckMate 901 Trial Data for Metastatic Bladder Cancer

Investigators evaluated treatment with Opdivo (nivolumab) plus Yervoy (ipilimumab) versus gemcitabine-carboplatin chemotherapy for previously untreated unresectable or metastatic urothelial carcinoma, according to Dr. Guru Sonpavde.

Final results from the cisplatin-ineligible patient population evaluated in the CheckMate 901 trial were shared at the 

Food and Drug Administration (FDA) has approved Opdivo

 in combination with chemotherapy for the first-line treatment of patients with unresectable or metastatic urothelial carcinoma in March 2024. This regulatory approval was generated by data 

To further discuss this topic, Sonpavde sat down for an interview with CURE live on site at the meeting to discuss how the results of the CheckMate 901 trial may influence discussions around starting immunotherapy versus standard chemotherapy in the treatment of patients with metastatic or unresectable urothelial cancer who cannot receive cisplatin.

Sonpavde serves as the medical director of genitourinary oncology, and is an assistant director of the Clinical Research Unit and the Christopher K. Glanz Chair for Bladder Cancer Research at the AdventHealth Cancer Institute, located in Orlando, Florida.

At the moment … we really cannot institute Opdivo plus Yervoy, since it's not going to be approved based on these data. Of course, being a negative trial for the Opdivo plus Yervoy comparison, I think it does provide some momentum to the strategy of combined PD-1 and CTLA-4 therapy for at least a subset of patients. Remember, the PD-1/CTLA-4 strategy is also being looked at in metastatic disease.

We are still awaiting a trial called the NILE trial, which is looking at platinum-based chemotherapy plus Imfinzi (durvalumab) and Imjudo (tremelimumab) for advanced disease. That trial also has a (gemcitabine)-platinum plus Imfinzi comparison with (gemcitabine)-platinum as the standard. Also, we have a potentially even more exciting neoadjuvant trial, which is looking at Imfinzi and Imjudo plus Padcev (enfortumab vedotin-ejfv).

So, I think there's still some scope for a PD-1 plus CTLA-4 inhibition combination coming into the clinic. We'll have to wait and see what the results of NILE and the neoadjuvant trial — that's the VOLGA trial — look like. Perhaps there's still some scope for that kind of double immune checkpoint inhibitor combination.

Transcript has been edited for clarity and conciseness.

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The CheckMate 901 trial evaluated Opdivo (nivolumab) plus Yervoy (ipilimumab) against gemcitabine-carboplatin chemotherapy for cisplatin-ineligible patients with unresectable or metastatic urothelial carcinoma. Despite the trial's negative outcome for the Opdivo-Yervoy combination, the FDA approved Opdivo with chemotherapy for first-line treatment in March 2024. Ongoing trials, such as the NILE and VOLGA trials, are exploring other combinations, including PD-1 and CTLA-4 inhibitors, which may influence future treatment strategies for advanced urothelial carcinoma.

Dr. Guru Sonpavde discusses the CheckMate 901 trial evaluating Opdivo plus Yervoy for those with cisplatin-ineligible, metastatic urothelial carcinoma.

Kristie L. Kahl

Understanding Breast Cancer Biomarkers Drives Patient Treatment Decisions

Zilovertamab Vedotin Plus Chemo Combo Shows Responses in R/R DLBCL

Addressing Complications from ADT Therapy to Treat Prostate Cancer

Breaking Down the CheckMate 901 Trial Data for Metastatic Bladder Cancer

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