Spencer Feldman

Sarclisa, a new drug, has been approved by the FDA for treating newly diagnosed, transplant-ineligible multiple myeloma patients, demonstrating a significant reduction in disease progression or death.

The Food and Drug Administration (FDA) has approved Sarclisa (isatuximab-irfc) with Velcade (bortezomib), Revlimid (lenalidomide) and dexamethasone, 

, for the treatment of adults with newly diagnosed multiple myeloma who are not eligible for autologous stem cell transplant (ASCT, when a patient’s own stem cells are collected, stored and infused back into them after treatment).

The efficacy of Sarclisa, the FDA announced, was determined in the IMROX phase 3 trial, which enrolled 446 patients to receive the Velcade, Revlimid and dexamethasone with or without Sarclisa.

In the trial, the Sarclisa regimen demonstrated a 40% reduction in the risk of disease progression or death. The median progression-free survival (PFS, the time a patient lives without their disease spreading or worsening) was not reached in the Isa-VRd arm, meaning fewer than half of the patients in that arm had experienced disease progression, and 54.3 months in the Sarclisa-free arm.

The most common side effects experienced by at least 20% of participants, the agency reported, were upper respiratory tract infection, diarrhea, fatigue, peripheral sensory neuropathy, pneumonia, musculoskeletal pain, cataract, constipation, peripheral edema, rash, infusion-related reaction, insomnia and COVID-19 infection.

 in combination with pomalidomide and dexamethasone for adults with multiple myeloma who received at least two prior therapies including lenalidomide and a proteasome inhibitor. 

 in combination with Kyprolis (carfilzomib) and dexamethasone to treat adults with relapsed or refractory multiple myeloma who have received one to three prior lines of therapy.

According to the National Cancer Institute, Sarclisa is a monoclonal antibody that binds to the protein CD38 found on some immune and cancer cells, including myeloma cells, and may block CD38 and help the immune system kill cancer cells.

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The Food and Drug Administration has approved Sarclisa as a first-line treatment for patients with multiple myeloma who are ineligible for autologous stem cell transplant.

FDA Approves Sarclisa In Newly Diagnosed Transplant-Ineligible Multiple Myeloma

The FDA has approved Rybrevant plus chemotherapy for certain patients with locally advanced or metastatic non-small cell lung cancer, following a presentation at the 2024 ESMO Congress. 

The Food and Drug Administration (FDA) has approved Rybrevant (amivantamab-vmjw) plus chemotherapy for patients with locally advanced or metastatic non-small cell lung cancer (NSCLC) with EGFR exon 19 deletions or L858R mutations.

Specifically, the approved treatment combination included Rybrevant plus carboplatin and pemetrexed chemotherapy. Eligible patients include those with locally advanced or metastatic NSCLC and EGFR exon 19 deletions or L858R mutations who have experienced disease progression (worsening or spreading) on or after receiving an EGFR tyrosine kinase inhibitor (TKI), according to the FDA’s alert.

The approval was based on the phase 3 MARIPOSA-2 trial, which evaluated the effectiveness of the Rybrevant-chemotherapy combination, in which researchers randomly assigned patients to three treatment groups. According to the alert, treatment groups included Rybrevant plus carboplatin and pemetrexed; carboplatin plus pemetrexed; or Rybrevant added to another combination regimen.

MARIPOSA-2 trial were recently presented at the 2024 ESMO Congress

Of note, the major outcomes measured in the trial included progression-free survival (PFS; time patients live without experiencing disease worsening or spreading) after the treatment with Rybrevant plus carboplatin and pemetrexed.

The secondary goals of the study were to determine the overall response rate (ORR; percentage of patients whose tumors shrunk or disappeared after treatment) and overall survival (OS; time patients live, regardless of their disease status).

Based on the results of the trial, the median PFS was 6.3 months in patients from the Rybrevant combination group versus 4.2 months in the carboplatin-pemetrexed group. The confirmed ORR was 53% and 29% in the Rybrevant combination and carboplatin-pemetrexed groups.

During a second interim analysis of OS, researchers reported that the OS was not statistically significant, with 85% of the deaths needed for the final analysis.

Regarding safety, the most common side effects that occurred in at least 20% or more patients included rash, infusion-related reactions, nail toxicity, nausea, fatigue, constipation, edema (swelling caused by fluid in tissues), stomatitis (inflammation of the mouth and lips), decrease in appetite, musculoskeletal pain (pain to the muscles or joints), vomiting and COVID-19 infection.

Recommended doses of Rybrevant plus carboplatin and pemetrexed is based on body weight at baseline, according to the alert.

The FDA has approved Rybrevant plus chemotherapy in certain patients with locally advanced or metastatic non-small cell lung cancer. 

Rybrevant Plus Chemo Approved by FDA in Lung Cancer Subset

Effective metastatic breast cancer management requires a multidisciplinary approach, strong patient-doctor communication, and tailored treatments based on biomarkers.

Although patients with metastatic breast cancer benefit from many factors including a multidisciplinary approach to care and thorough education to make treatment decisions, one of the most critical tools throughout this entire process is communication between patients and their care teams, an expert said.

 in Metastatic Breast Cancer, a panel of experts from Miami Cancer Institute in Florida discussed the space including information on initial and subsequent treatments, biomarkers and other areas that may be helpful for patients with the disease.

CURE also spoke with Dr. Jane Emilie Mendez, chief of breast surgery at Miami Cancer Institute in Florida, who chaired the event, to learn more about how information like this can be beneficial for patient outcomes.

“[Cancer isn’t] one street,” Mendez said in an interview with CURE. “It’s not your doctor wants to do this and that's that, because we need to know that we're keeping a balance between our efforts to cure you — at least keep your metastatic disease at bay — and your quality of life. … Even [if] we're keeping the cancer at bay but you're miserable with the side effects, what have we gained? … Ultimately, it's all about quality [of life].

Mendez added that multidisciplinary care that is often applied to patients with metastatic breast cancer is not “one size fits all.”

“We need to tailor the therapy to the specific characteristics of the tumor,” she said. “We have now so many ways that we can do that, either with tissue biopsy or liquid biopsy (with blood), tissue sampling, and how far we’ve come in terms of trying to better define all the subtleties about the tumors.”

With the identification of biomarkers, cancer teams can steer the treatment of patients with metastatic breast cancer in a direct that may be more effective.

“What are the characteristics within the particular tumor that the patient has that will allow us this ability to look for other potential treatments once they failed the standard and the minimally invasive [option],” Mendez said in an interview.

Even though treatment often starts with hormone therapy, which is minimally invasive and is often tolerated the best before systemic treatments, Mendez said, tumors may mutate over time. Thus, tumors should be checked periodically for any changes in biomarkers.

“It’s really more important to check that the tumor hasn’t mutated,” Mendez said. “And that will open the ability for us to find other potential treatments for the patient. It’s an ever-evolving trajectory. We cannot assume, and each patient is unique as well as their cancer. So those continued biopsies, when indicated, we see progression, that's our avenue for what else can we use.”

Knowing all of this information while navigating the treatment landscape of metastatic breast cancer is help so that patients can advocate for themselves and feel empowered along the way.

“[Patients should] know, if they're at a place that they're not seeing this type of activity or this type of [treatment] flow, they can seek out other opportunities so that they can get what's best for them, given their circumstances,” Mendez said. “At least be aware, because knowledge is power.”

Even with education, there may be a risk of overwhelming patients with information, some of which may also be misinformation.

“If [patients are] tech savvy, they can go to the computer, but a lot of [the information] might not be applicable to them, but be misinformation,” Mendez said. “And how do you know, as a patient, to discern what's real and what's not? And how do we, as people who are in the business, control that? Dr. Google is very famous, so that's a big problem that we have.”

In addition to misinformation, the educational material patients read should also be tailored to their educational level.

“There’s a lot of people who don’t even understand the word ‘cancer,’” Mendez said. “So how do you simplify that information so that they get it, and they can feel even that they have power with what’s happening to their body. It’s really hard.” 

Building Confidence to Discuss Side Effects

Patients have many members on their care team including the oncologist, the advanced practice provider (like nurse practitioners), a nurse and patient navigators, in some instances. As long as patients voice any concerns — no matter how big or small they may seem — to someone on that team, it should be then discussed with the member of the team who makes treatment decisions. 

Mendez said that patients should feel comfortable to discuss their side effects, ask questions and communicate with their team, even though some patients may be like to discuss their concerns than others.

“Not all patients have the same needs,” she said. “Some patients are very, very self-sufficient, and they'll be very vocal. It's more about the patient who doesn't want to impose upon the doctor. They feel that they would be bothering the doctor by calling. But in reality, if we don't know, we cannot do anything about it.”

Once made aware of any concerns, care teams may be able to help address them either with pharmaceutical modalities or even adjusting doses of the cancer treatments.

“A lot of these side effects occur not when you're at the doctor's office; they occur when you're taking the medication at home,” Mendez said. “You might be having dehydration. You might have diarrhea. You might be having fatigue. You don't want to do anything. You might be depressed. Whatever the reason might be, if we don't know, how can we change that or adjust the treatment to make it more palatable for the patient?”

Through communication and education, patients with metastatic breast cancer may be able to balance treatment with quality of life. 

Navigating the ‘Ever-Evolving Trajectory’ of Metastatic Breast Cancer

Trodelvy shows promise as a potential treatment option for patients with advanced or metastatic bladder cancer who have progressed after checkpoint inhibitor therapy.

Trodelvy (sacituzumab govitecan) demonstrated a relatively high response rate with rapid responses in patients with locally advanced (cancer that has spread beyond its original size) or metastatic (disease that spread to other areas) urothelial cancer, a type of bladder cancer, according to a study.

In the TROPHY-U-01 trial published in the 

, at a median follow-up of 9.3 months, patients demonstrated an overall response rate (percentage of people whose disease shrinks or disappears after treatment) of 32%, a clinical benefit rate (the percentage of patients who show improvement in their cancer after treatment) of 42%, median duration of response (the time from treatment until the disease progresses or the patient dies) of 5.6 months, median progression-free survival (how long a person lives without their disease getting worse) of 5.6 months and a median overall survival (the time from the start of treatment when a patient with cancer is still alive) of 13.5 months.

Patients that were included in the study had locally advanced or metastatic urothelial cancer whose disease progressed or recurred after a checkpoint inhibitor (this blocks certain proteins that cancer cells use to evade the immune response) and who were ineligible for cisplatin.

Some of the factors that determined whether a patient was ineligible for cisplatin included moderate functional impairment (assessed by the ECOG performance score), impaired kidney or heart function, and significant hearing loss or peripheral neuropathy (nerve pain, numbness, tingling, swelling or muscle weakness.

This trial included 38 patients (61% men) with a median age of 72.5 years. Among patients in the trial, 66% (25 patients) has visceral metastasis (disease that spread within the body cavity such as the abdomen or chest), of whom 29% (11 patients) had disease that metastasized to the liver. Fifty percent of patients received previous platinum-based chemotherapy as either neoadjuvant (first step to shrink a tumor before the main treatment) or adjuvant therapy (additional treatment given after the initial treatment to lower the risk for recurrence).

Patients in the study were treated with Trodelvy on days one and eight of a 21-day cycle. Treatment continued until disease progression, informed consent withdrawal and unacceptable side effects. Patients were allowed a five-week maximum break (decided upon by their cancer team) from treatment to recover from any harmful side effect.

The primary focus of the study was overall response rate. Secondary endpoints included duration of response, clinical benefit rate, progression-free survival and safety.

All 38 patients in the trial experienced at least one side effect from the treatment. Of note, 33 (87%) had at least a grade 3 (severe) side effect. The most common treatment-induced side effects of any grade included diarrhea (66%), fatigue (50%), nausea (53%), hair loss (50%), neutropenia (lower-than-normal number of neutrophils, a type of white blood cell; 45%), constipation (40%), leukopenia (low levels of leukocytes, a type of white blood cell; 34%) and decreased appetite (32%). These treatment-related side effects resulted in the interruption of Trodelvy treatment in 61% of patients, dose reduction in 37% and the discontinuation of Trodelvy in 21% of patients. Treatment discontinuation was attributed to diarrhea (2 patients), febrile neutropenia (fever with a low levels of neutrophils; 1 patient), colitis (inflammation of the colon; 1 patient), vomiting (1 patient), nausea (1 patient), fever (1 patient), weakness (1 patient), pneumonia (1 patient), sepsis (an extreme immune response to an infection that may lead to organ failure, tissue damage or death if not immediately treated; 1 patient) and maculopapular rash (a skin rash with a combination of flat, discolored areas and raised bumps; 1 patient).

“ [Trodelvy] demonstrated a relatively high [overall response rate] with manageable toxicity profile in cisplatin-ineligible patients with progression after [checkpoint inhibitors]. These data warrant further evaluation of [Trodelvy] (alone and in combinations) in [locally advanced]/mUC,” study authors concluded.

Trodelvy in locally advanced or metastatic urothelial cancer may provide another option for those whose disease progressed after checkpoint inhibitors. 

Spencer Feldman

FDA Approves Sarclisa In Newly Diagnosed Transplant-Ineligible Multiple Myeloma

Rybrevant Plus Chemo Approved by FDA in Lung Cancer Subset

Navigating the ‘Ever-Evolving Trajectory’ of Metastatic Breast Cancer

Trodelvy May Improve Responses in Bladder Cancer Subtype

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