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While scientists have a limited understanding of how brain metastases genetically evolve from their primary tumor, research presented at the Society for Neuro-Oncology’s Annual Meeting may have identified a connection between genetic mutations and treatment options that could offer patients improved outcomes.

Common Mutations Could Lead to Targeted Treatment for Patients with Brain Metastases

Continuous advances in treatment for patients with relapsed or refractory multiple myeloma emphasize the need for patients and their doctors to work together during treatment decision-making.

Considering factors such as disease-free survival may be important for patients. However, quality of life and family circumstances should also be carefully thought out before treatment decisions are made, said Dr. Henry Fung during an interview with CURE®.

Fung is the chair of the Department of Bone Marrow Transplant and Cellular Therapies and director of the Multiple Myeloma Programs at Fox Chase Cancer Center in Philadelphia.

He recently sat down with CURE® to discuss available treatment options for patients with relapsed or refractory multiple myeloma, why collective treatment decisions are crucial and advice for patients, regardless of the status of their journey.

CURE®: For patients with relapsed or refractory multiple myeloma, what are some of the traditional treatments they may receive?

There are many treatment options for patients with relapsed or refractory multiple myeloma. Unfortunately, all patients will [experience] relapse with multiple myeloma. We still consider multiple myeloma an incurable disease, but it’s also not uncommon for patients to be disease-free or in remission beyond seven to eight years. We’ve had patients go beyond 15 years and are still disease-free, so maybe this is potentially curable, but we don’t have enough data to declare that yet.

The first treatment includes the anti-CD38 monoclonal antibody, which should be included in every single salvage regimen nowadays and also has recently become the standard of care for frontline treatment.

Then, we have three different immunomodulating agents: [Thalomid (thalidomide)], [Pomalyst (pomalidomide)] and [Revlimid (lenalidomide)].

The combination [of treatments] that we will use will depend on whether patients are refractory to the last treatment. Also, the toxicity profile [is important], and that will determine the treatment for patients.

Having said that, these [treatments] are also evolving very rapidly. Now we have two CAR-T cell therapies and three bispecific antibodies.

Do patients have a say in what treatment or treatment combination they receive for their relapsed or refractory multiple myeloma?

Yes, we always give them the option while we’re [deciding on treatment]. We need to get patients’ informed consent and [understand] what the goal of therapy is for each patient.

Then, based on our expertise, [we list] what is best for [the patient]. [We ask] what they think and the alternative options. The goal of therapy is different for everyone. There are patients who say, “I want to at least play nine-hole golf. Otherwise, I don’t want to live anymore.” So, everyone’s goals are different: family goals are different and patient goals are different.

[Factors are considered, such as] whether they need pain medication, whether it’s worth continuing treatment, if they can be disease-free, if it’s important to reach remission or if they can just live as long as possible.

KRd56 Versus KRd27 Shows Similar Effectiveness, Safety in R/R Multiple Myeloma

For CAR-T cell therapy, it’s a one-time treatment, and if it works well, patients can be disease-free for a few years or more than that. [Patients] may live for three years or five years, but in between, one can play 18-hole golf, and the other has to come to see us every week.

Some patients want potentially fewer side effects. The CAR-T cell therapy is more intensive and has more side effects. [Some patients might say,] “I don’t want to take the risk, I don’t want to do that. I love the nurses and doctors so much.” So, they’ll come to the office. So, there are many considerations.

What advice would you offer to patients with relapsed or refractory multiple myeloma?

I think it’s very important for patients with newly diagnosed multiple myeloma or [patients] at any [point] of disease progression should connect with a myeloma center for multiple myeloma. [These centers] have the expertise and support for them and [they can] work with their local doctors together in order to get the best treatment.

Everyone should have a second opinion. As we said there are many [treatment] options. It’s good that [patients may] respect and trust their doctor, but now there are many different treatment options to choose from. All patients deserve the best, not just to live. They all deserve the best treatment, not just to [have good] responses to or reach remission or make them live longer. Because there are different options, the goal of therapy should be discussed, [considering] what patients think is best for them, their family and their circumstances.

This transcription was edited for clarity and conciseness.

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Advancements in treating relapsed or refractory multiple myeloma necessitate collaborative decision-making between patients and physicians, considering both clinical outcomes and personal circumstances. While multiple myeloma remains incurable, long-term remission is possible with evolving treatments like anti-CD38 monoclonal antibodies, immunomodulating agents, CAR-T cell therapies, and bispecific antibodies. Patients should be actively involved in treatment choices, aligning therapy goals with personal and family priorities. Seeking care from specialized myeloma centers and obtaining second opinions are crucial for optimizing treatment strategies and ensuring the best possible outcomes.

Patients with relapsed or refractory multiple myeloma should consider quality of life with survival when choosing the most suitable treatment option.

Tumor

QOL a Crucial Consideration During R/R Myeloma Treatment Decision-Making

The time to testosterone recovery in patients with prostate cancer depends on factors including length of androgen deprivation therapy (ADT), testosterone levels before treatment and age.

included 1,444 patients with prostate cancer from five trials. Among the overall patient population, researchers treated 115 with ADT for four months, treated 880 for six months, treated 353 for 18 months, treated 36 for 28 months and treated 60 for 36 months. Of note, patients who received ADT for longer periods had more aggressive prostate cancer, senior study author Dr. Amar Kishan explained to CURE®.

Kishan is a radiation oncologist and the executive vice chair for the Department of Radiation Oncology at the David Geffen School of Medicine at UCLA and the UCLA Jonsson Comprehensive Cancer Center in Los Angeles.

“What we wanted to look at is whether we could identify two things. The first is patterns and predictors of recovering testosterone,” he said. “The second is whether there is any association between how long it takes to recover testosterone and the ultimate cure rates or outcomes.”

Testosterone Recovery in Patients With Prostate Cancer

After treatment for prostate cancer, it’s common for patients to 

. However, a common complaint related to side effects includes having lower levels of testosterone, Kishan noted.

“A side effect that patients are bothered by is the low testosterone levels because it has that consolation of side effects,” he said. “The key is this is intended to be temporary. We’re not trying to permanently suppress testosterone levels — [just] temporarily to help treat the prostate cancer.”

Researchers established from the findings that patients with higher baseline testosterone levels and who were younger were more likely to recover testosterone. The variability in testosterone recovery, Kishan said, was surprising to him and his co-authors.

“One was [patients’] baseline testosterone,” he explained. “So it is intuitive, but a patient with a higher baseline testosterone actually recovers testosterone much more quickly than someone who maybe has a lower testosterone baseline.

“Younger men [also] tend to recover testosterone much more quickly than older men. So, we had maybe hypothesized that that would be the case, but the magnitude of those effects is pretty significant, and that was interesting to us.”

Kishan explained that the average time is approximately six months, “which is good," regarding the specific timing for testosterone recovery. The rate of recovery surpassing 18 months means it may take a bit longer for testosterone recovery, he said.

“Not everyone recovers at the same time,” Kishan also noted. “There may be men who, even six months after they've stopped hormone therapy, have not begun to recover testosterone.”

Side Effects of ADT and Management in Patients With Prostate Cancer

Some common side effects associated with ADT for prostate cancer include loss of libido, hot flashes, weight gain, decreased bone density, insulin resistance and mood disturbances, according to Kishan.

“There are a lot of potential side effects,” he explained. “It’s often like a landmark event for someone to recover their testosterone after going through this long period of testosterone suppression.”

Although this side effect can be particularly frustrating, Kishan emphasized that patients should avoid doing something extra to recover unnaturally.

“I tell patients in the beginning … it’s at least six months on average to start to recover testosterone after getting six months of hormone therapy,” he said. “In that first six months, it’s unlikely for someone to recover and we don’t want someone to do something extra to recover. We want them to take that time to naturally recover.”

Kishan noted that unless patients are demonstrating signs of no recovery, they typically do not receive testosterone replacement therapy. Nonetheless, “most patients do recover. It is variable from patient to patient and it’s certainly frustrating.”

For patients who are looking to further mitigate side effects of ADT, Kishan recommended patients discuss options with their doctors.

“It’s totally normal to feel disappointed with the side effects,” he said. “Be open with providers about any side effects that are experienced, whether there may be prescription medications or lifestyle changes like exercise, [taking] calcium supplements, or something that could help mitigate some of the side effects.”

Testosterone recovery in prostate cancer patients post-ADT is influenced by treatment duration, baseline testosterone levels, and age. A study involving 1,444 patients revealed that longer ADT duration correlates with more aggressive cancer. Younger patients and those with higher baseline testosterone recover faster. Recovery typically takes around six months, but can extend beyond 18 months. ADT side effects include low libido, hot flashes, and mood changes. Patients are advised against hastening recovery unnaturally and should consult doctors for managing side effects through lifestyle changes or medications.

Patients with prostate cancer may differ in time to testosterone recovery, depending on the length of treatment and age, but takes six months on average.

Testosterone Recovery in Prostate Cancer May Depend on ADT Intensity

Among patients with cancer beginning regular treatment with opioids for pain relief, administration of Symproic (naldemedine) has been found to potentially prevent constipation, improve constipation-related quality of life and possibly prevent opioid-induced nausea and vomiting, research has shown.

Study findings from 99 patients at four academic hospitals in Japan were published in the 

Dr. Jun Hamano, study co-author and assistant professor in the Institute of Medicine at the University of Tsukuba in Japan, where he is part of the Center for Medical Liaison and Patient Support Service as well as the Center for Palliative and Supportive Care, told CURE® via email that constipation occurs in 63% to 81% of patients with cancer receiving opioids.

The study, conducted between July 2, 2021 and May 30, 2023, included patients with cancer ages 20 years and older who were starting strong opioid therapy. Patients received either 0.2 milligrams of Symproic (49 patients) once a day after breakfast for 14 days or placebo (50 patients), also once a day after breakfast for 14 days.

Researchers primarily evaluated patients’ responses via the Bowel Function Index (BFI), which they described as a three-item subjective scale developed for opioid-induced constipation, where patients estimate their ease of defecation, their feeling of incomplete bowel evacuation and their personal judgement of constipation, each on a scale of 0 to 100 with the mean of those three scores being the total score. The total score can range from 0 to 100, with higher scores indicating more severe constipation.

According to the study findings, significantly more patients in the Symproic group had a BFI of less than 28.8 on day 14 (64.6%) compared to the patients in the placebo group (17%), with a 47.6% difference between the two groups.

Likewise, after seven days 58.3% of patients in the Symproic group had a BFI of less than 28.8, compared to 17% of the patients in the placebo group.

Regarding spontaneous bowel movements, after seven days 85.4% of the Symproic group experienced at least three per week, versus 51.1% of the placebo group. In the Symproic group, 72.9% of patients have at least three complete spontaneous bowel movements at day 7, versus 36.2% of patients in the placebo group. Similarly, by day 14 87.5% of patients in the Symproic group and 53.2% of patients in the placebo group had experienced at least three spontaneous bowel movements per week, while 70.8% and 36.2% of patients, respectively, experienced at least three complete spontaneous bowel movements per week.

Use of Symproic, researchers further noted, was also associated with improved patient-reported quality of life and reduced incidence of opioid-induced nausea and vomiting when compared to patients who received placebo.

“Many [patients with cancer] require opioids for symptom relief,” Hamano said. “It is also known that many people become constipated and their quality of life declines as a result of opioid use. Therefore, our research results provide insights that can be used to improve the quality of life of cancer patients who require opioid-based symptom relief.”

Hamano stressed that, when speaking with their care providers, “it is necessary [for patients] to regularly discuss changes in bowel habits and the level of satisfaction with defecation.”

“Preventive use of [Symproic] for opioid-induced constipation may be considered, although further studies are needed to assess longer term effects and to compare with less costly alternatives,” wrote Dr. Camilla Zimmerman, an associate editor of the 

For more news on cancer updates, research and education, don’t forget to 

Symproic (naldemedine) has shown promise in preventing opioid-induced constipation and improving related quality of life in cancer patients starting opioid therapy. A study involving 99 patients across four Japanese hospitals demonstrated that those receiving Symproic had significantly better bowel function scores and more frequent spontaneous bowel movements compared to a placebo group. Additionally, Symproic was associated with reduced opioid-induced nausea and vomiting. While results are promising, further research is needed to evaluate long-term effects and cost-effectiveness compared to other treatments.

For patients with cancer, Symproic may prevent constipation and improve quality of life.

Side Effect Management

Symproic May Prevent Opioid-Induced Constipation

The combination of avutometinib and defactinib has been found to be effective among patients with recurrent low-grade serous ovarian cancer (LGSOC), updated clinical trial data has shown.

Updated findings from the phase 2 RAMP 201 clinical trial, presented as part of the International Gynecologic Cancer Society 2024 Annual Meeting, showed that patients treated with the combination experienced a median progression-free survival (PFS) of more than a year, according to a news release from biopharmaceutical company Verastem Oncology.

Based on the findings of the RAMP 201 trial, Verastem Oncology plans to submit a New Drug Application to the Food and Drug Administration (FDA) in October 2024 for adults with recurrent KRAS-mutant LGSOC who have received at least one prior systemic therapy, and also plans to seek accelerated approval from the agency and will request priority review, according to the news release.

While the current standard of care for the cancer type includes hormone therapy and chemotherapy, Verastem Oncology president and chief executive officer Dan Paterson said in the news release that this would mark the first FDA-approved treatment for patients with recurrent KRAS-mutant LGSOC. The company hopes to make the treatment commercially available in the United States in 2025.

"In the mature data from the RAMP 201 trial, most patients achieved tumor reductions and a median progression-free survival that was greater than one year across both KRAS-mutant and KRAS-wild-type patient populations. These results reinforce our confidence in the potential of the combination of avutometinib and defactinib to change how patients with recurrent low-grade serous ovarian cancer are treated," stated Dr. John Hayslip, chief medical officer of Verastem Oncology, in the news release. "Encouraged by the durable clinical benefit seen in KRAS-wild-type patients in RAMP 201 and the poorer prognosis in this subset of patients that are treated with sub-optimal treatment choices today, we believe that this treatment combination will be the preferred treatment option for all subgroups of patients with recurrent low-grade serous ovarian cancer. We are committed to making the combination available to these patients, including working with the FDA to outline a path forward to expand the indication with additional data."

At a data cut-off of June 30, 2024, primary analysis of the RAMP 201 trial showed an objective response rate (ORR) in all evaluable patients with approximately 12 months of follow-up. The confirmed response was 44% among patients with KRAS-mutant LGSOC and 17% for patients with KRAS-wild-type LGSOC.

Among all patients, the median duration of response was 31.1 months, with it being 31.1 months in the KRAS-mutant patients and 9.2 months in patients with KRAS wild-type LGSOC.

Of note, the median PFS was 12.9 months among all patients, 22 months for patients with KRAS-mutant LGSOC and 12.8 months among those with KRAS wild-type LGSOC.

The disease control rate (DCR) at six or more months was 61% in all patients, 70% in patients with KRAS mutations and 50% in patients with the KRAS wild-type LGSOC.

The news release noted that there was a 10% discontinuation rate due to side effects, with no new safety signals observed. The most common side effects in all grades and grade 3 (severe) or higher were nausea (67%, 2.6%), diarrhea (58.3%, 7.8%) and increased blood creatine phosphokinase levels (60%, 24.3%).

"The notable response rates and low discontinuation rate seen with the combination of avutometinib and defactinib are significant. These updated results confirm the potential of this new combination therapy to change practice and be the new standard for care for recurrent low-grade serous ovarian cancer, which previously had limited effective treatment options," stated professor Susana Banerjee, global lead investigator of the study, consultant medical oncologist at The Royal Marsden NHS Foundation Trust and team leader in women’s cancers at The Institute of Cancer Research in London.

The combination of avutometinib and defactinib has shown promising efficacy in treating recurrent low-grade serous ovarian cancer (LGSOC), with a median progression-free survival (PFS) exceeding one year. The RAMP 201 trial results indicate a 44% response rate in KRAS-mutant patients and 17% in KRAS-wild-type patients. Verastem Oncology plans to submit a New Drug Application to the FDA, aiming for accelerated approval. The treatment could become the first FDA-approved option for recurrent KRAS-mutant LGSOC, with commercial availability anticipated in 2025.

Results from the RAMP 201 clinical trial are promising for patients with recurrent low-grade serous ovarian cancer.

Avutometinib and Defactinib May Benefit Some with Ovarian Cancer

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