Spencer Feldman

The FDA approved Braftovi plus Erbitux and mFOLFOX6 to treat patients with metastatic colorectal cancer with a BRAF V600E mutation.

The Food and Drug Administration (FDA) approved Braftovi (encorafenib) plus Erbitux (cetuximab) and mFOLFOX6 to treat patients with metastatic colorectal cancer with a BRAF V600E mutation.

mFOLFOX6 is a chemotherapy regimen consisting of oxaliplatin plus leucovorin plus fluorouracil, according to the FDA.

The accelerated approval, which was announced by an alert from the FDA, was based on findings from the BREAKWATER trial. The trial included patients with treatment naïve BRAF V600E mutation-positive metastatic colorectal cancer detected by an FDA-approved test, particularly the Qiagen therascreen BRAF V600E RGQ polymerase chain reaction kit.

Objective response rate: the percentage of patients with a partial or complete response to treatment.

Progression-free survival: the time during and after treatment when a patient with cancer lives with the disease without worsening.

Overall survival: the time from diagnosis or start of treatment when a patient with cancer is still alive.

Decreased neutrophil counts: lower than normal number of neutrophils, a type of white blood cell, which, when decreased, can impact the body’s ability to fight off infections.

Increased lipase counts: a higher level of an enzyme in the blood that is produced by the pancreas. Increased levels may indicate pancreatitis or other gastrointestinal problems.

Initially, patients were randomly assigned to receive either Braftovi with Erbitux every two weeks; Braftovi with Erbitux and mFOLFOX6 every two weeks; or mFOLFOX6, FOLFOXIRI (both every two weeks) or CAPOX (every three weeks). The last arm’s treatment was administered either with or without Avastin (bevacizumab). Eventually the trial was updated to only include the first two treatment assignments.

Patients were treated until unacceptable toxicity, disease progression, lost to follow-up, consent withdrawal or death, according to the alert. The approval was mainly based on results in patients assigned Braftovi with Erbitux and mFOLFOX6 compared with those treated with mFOLFOX6, FOLFOXIRI or CAPOX, which defined the control arm.

The main area of interest was objective response rate. In the trial, the objective response rate was 61% in patients treated with Braftovi with Erbitux and mFOLFOX6 compared with 40% in those in the control arm. The median duration of response was 13.9 months in the treatment arm and 11.1 months in the control arm.

Researchers will also be assessing overall survival and progression-free survival in the ongoing BREAKWATER trial as part of the post-marketing confirmatory evidence for this accelerated approval, according to the alert.

The most common side effects, which occurred in at least 25% of patients, included nausea, peripheral neuropathy, rash, fatigue, diarrhea, vomiting, decreased appetite, abdominal pain, bleeding and fever. In addition, the most common grade 3 (severe) or 4 (life-threatening) laboratory abnormalities, occurring in at least 20% of patients, were decreased neutrophil counts and increased lipase counts.

The FDA noted that the recommended dose of Braftovi is 300 milligrams, administered orally (via four 75-milligram capsules) once per day plus Erbitux and mFOLFOX6 until disease progression or unacceptable toxicity.

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Articles

The FDA has granted accelerated approval for the combination of Braftovi (encorafenib), Erbitux (cetuximab), and mFOLFOX6 to treat metastatic colorectal cancer with a BRAF V600E mutation. This decision is based on the BREAKWATER trial, which demonstrated a 61% objective response rate for the treatment group compared to 40% for the control group. The trial also reported a median response duration of 13.9 months. Common side effects include nausea, peripheral neuropathy, and severe laboratory abnormalities like decreased neutrophil counts.

Braftovi received accelerated approval with Erbitux and mFOLFOX6 for metastatic colorectal cancer with a BRAF V600E mutation. 

FDA Approves Braftovi Plus Erbitux and Chemo for Metastatic Colorectal Cancer Subset

UGN-102 has shown promising results as a non-surgical alternative for patients with recurrent low-grade intermediate-risk non-muscle-invasive bladder cancer.

For patients with recurrent low-grade intermediate-risk non-muscle-invasive bladder cancer, treatment with the novel UGN-102 has shown better responses versus traditional treatment of transurethral resection of bladder tumor (TURBT).

These treatment comparisons were based on the ENVISION study published in 

, which evaluated UGN-102 in patients with recurrent low-grade intermediate-risk non-muscle invasive bladder cancer. Although UGN-102 has not been approved by the Food and Drug Administration (FDA), the treatment may have a positive impact on health and quality of life, an expert said.

In the study, 240 patients were treated with UGN-102 and had a 79.6% complete response rate at three months after the first treatment with UGN-102, explained Dr. Sandip Prasad in an email interview with CURE®.

Prasad is a urologist at Atlantic Medical Group in Morristown, New Jersey.

CURE® spoke with Prasad to discuss the effectiveness of UGN-102, how it compares with standard of care, what patients should know regarding side effects and the treatment’s potential.

Transurethral resection of bladder tumor (TURBT): a surgery that removes bladder tumors.

UGN-102: a non-surgical intervention in a gel form to help treat low-grade intermediate-risk non-muscle-invasive bladder cancer.

Complete response rate: percentage of patients who show no signs or symptoms of cancer after receiving treatment.

Fulguration: a type of treatment that utilizes electrical currents to destroy cancer cells.

Cystoscopy: a procedure where a doctor examines the lining of the bladder and the urethra, the tube that carries out urine.

CURE®: What does this research mean for patients with recurrent low-grade intermediate-risk non-muscle-invasive bladder cancer and how might it affect their treatment options?

: Currently, there are no other options for these patients for primary treatment other than TURBT or office fulguration. Both of these involve cystoscopy and can result in associated complications with this procedure. If UGN-102 is approved [by the FDA], it would serve as a primary non-surgical option for these highly recurrent patients.

What are some traditional treatments specifically for patients with non-muscle-invasive bladder cancer?

Traditional treatments include TURBT (performed under anesthesia and with discontinuation of blood thinners) or office fulguration, which can be uncomfortable for patients and may not completely destroy the tumor. Both of these often have the associated side effects seen with cystoscopy, including [urinary tract infection (UTI)], hematuria (blood in urine) and dysuria (pain while urination). For intermediate-risk patients, follow-up adjuvant treatment may also include intravesical chemotherapy (or less commonly, intravesical immunotherapy).

How do these traditional treatments compare or contrast with UGN-102?

UGN-102 does not require cystoscopy, anesthesia or discontinuation of blood products. The chemoablative gel is instilled via a urethral catheter, which can be performed in minutes in the office. The catheter is then removed and patients can go home.

UGN-102 Shows Promising Treatment Responses in Recurrent Bladder Cancer

What are some of the side effects associated with UGN-102?

The side effects seen in the three phase 2/3 studies with UGN-102 were those commonly seen with all intravesical treatments and include hematuria, dysuria, UTI and urinary frequency or urgency. The vast majority were mild to moderate, with only two severe treatment-related side effects noted, which were urinary retention and urethral stenosis (narrowing of the urethra), both of which resolved.

Is there anything patients can do to help mitigate or manage some of these side effects on their own?

We encourage hydration as one of the advantages of the reverse thermal gel mechanism of UGN-102 is that it is not excreted with the first void like aqueous intravesical chemotherapy. Patients can also pre-treat with over-the-counter medications to help with mild irritative symptoms but these are typically mild, if present.

What advice would you offer to this patient population regarding treatment with UGN-102?

UGN-102 is not an approved agent yet, so outside of clinical trials, is unavailable at this time. The 

 for UGN-102 was accepted by the FDA and a PDUFA target action date was set for June 2025. If approved, UGN-102 would be an additional tool in the armamentarium of the urologist in the treatment of this recurrent cancer which can impact health and quality of life. 

Transcript was edited for clarity and conciseness.

“Primary Chemoablation of Recurrent Low-Grade Intermediate-Risk Nonmuscle-Invasive Bladder Cancer With UGN-102: A Single-Arm, Open-Label, Phase 3 Trial (ENVISION)” by Dr. Sandip M. Prasad, et al., 

UGN-102, a novel treatment for recurrent low-grade intermediate-risk non-muscle-invasive bladder cancer, has demonstrated superior response rates compared to traditional TURBT. The ENVISION study reported a 79.6% complete response rate at three months post-treatment with UGN-102. Unlike traditional methods, UGN-102 does not require cystoscopy or anesthesia, offering a less invasive option. Common side effects are mild to moderate, including hematuria and dysuria. Although not yet FDA-approved, UGN-102 could become a significant non-surgical treatment option if approved by June 2025.

Treatment with UGN-102 has shown promise as a non-surgical alternative when compared with a surgical approach for certain patients with bladder cancer. 

UGN-102 May Improve Quality of Life Versus Surgery in Bladder Cancer

CURE® spoke with an expert about follicular lymphoma, a disease that is still considered incurable.

What is Follicular Lymphoma and Why Are Better Treatments Needed?

There have been a number of advancements in the treatment of follicular lymphoma in 2024.

, the Food and Drug Administration (FDA) approved Brukinsa (zanubrutinib) plus Gazyva (obinutuzumab) for the treatment of patients with relapsed or refractory follicular lymphoma who had undergone two or more prior lines of systemic therapy. This approval was followed 

 by the FDA’s approval of Breyanzi (lisocabtagene maraleucel) for the treatment of patients with relapsed or refractory follicular lymphoma who had previously been treated with two or more lines of therapy and 

 by the agency’s granting of an accelerated approval to Epkinly (epcoritamab-bysp) for patients with relapsed or refractory follicular lymphoma who have been previously treated with two or more lines of systemic therapy.

Additionally, Monjuvi (tafasitamab) has been shown to have positive results regarding disease progression for patients with relapsed or refractory follicular lymphoma, with Monjuvi manufacturer Incyte announcing 

 that it plans to file a supplemental Biologics License Application with the FDA for Monjuvi to treat patients with follicular lymphoma who previously underwent at least one previous systemic anti-CD20 immunotherapy or chemo-immunotherapy.

During the 2024 American Society of Hematology Annual Meeting and Exposition, CURE® spoke with Dr. Christina Poh, a physician at the Fred Hutch Cancer Center and an assistant professor in the Division of Hematology and Oncology, University of Washington School of Medicine about follicular lymphoma and the need for better treatments.

The nature of follicular lymphoma lies in the underlying pathogenesis. Essentially, this is a disease that is generally indolent, so it's generally slow growing, waxing and waning, but currently with our available therapies, it's still considered incurable, and so especially for our patients who are diagnosed at a younger age, there is a need for better therapies, or more therapies that will essentially prolong, that will help get the disease under control and actually control the disease for a long time. Ideally, we want this condition, obviously, to be curable. We want to be able to cure this, but I think at the end of the day, we want to make sure that this does not harm our patients or cause complications with their daily life.

Transcript has been edited for clarity and conciseness.

Videos

The FDA has approved Ensacove for patients with ALK-positive locally advanced or metastatic non-small cell lung cancer who have not previously received an ALK-inhibitor.

The Food and Drug Administration has approved Ensacove (ensartinib) for the treatment of adults with anaplastic lymphoma kinase (ALK)-positive locally advanced or metastatic non-small cell lung cancer (NSCLC) who have not previously received an ALK-inhibitor, the agency has announced.

The efficacy of Ensacove was demonstrated in the phase 3 eXALT3 clinical trial of 290 patients with locally advanced or metastatic 

 who had not previously received an ALK-targeted therapy, with patients being evenly randomized to receive Ensacove or Xalkori (crizotinib).

“Our ALK Positive lung cancer community is grateful for the scientists, investigators, patients and [Ensacove manufacturer] Xcovery for bringing another treatment option to our community. Hopefully, the availability of Ensacove will further extend the lives of ALK-positive lung cancer patients!” Dr. Ken Culver, director of research and clinical affairs for the organization ALK Positive, told CURE® via email. 

Progression-free survival: the time a patient lives without their disease spreading or worsening.

Overall survival: the time a patient lives, regardless of disease status.

Edema: swelling caused by a buildup of fluid.

Findings from the trial were published in 

 Oncology in 2021, where Ensacove was found to result in what researchers described as a statistically significant improvement in progression-free survival (PFS) compared to Xalkori, with the median PFS times being 25.8 months and 12.7 months, respectively.

“[Ensacove] represents a new first-line treatment option for patients with ALK-positive NSCLC,” researchers stated in the study.

However, the FDA noted in its approval announcement that there was no statistically significant difference regarding overall survival.

The most common side effects experienced by at least 20% of patients were rash, musculoskeletal pain, constipation, cough, pruritis, nausea, edema, pyrexia and fatigue.

According to the agency, the recommended dose is 225 mg orally daily, with or without food, until disease progression or unacceptable toxicity.

 that there are between 90 and 100 current clinical trials in the United States and the European Union allowing patients with ALK-positive NSCLC, with 15 or so being for treatments specifically designed to target ALK-positive disease.

There are approximately 10,000 new cases of ALK-positive lung cancer each year, with an average survival of seven years and approximately 70,000 patients with ALK-positive lung cancer currently living in the United States, Culver said.

ALK fusions exist in 3% to 5% of patients with NSCLC, Dr. Stephen Liu, a medical oncologist who leads the Thoracic Oncology and the Developmental Therapeutics sections at Georgetown University’s Lombardi Comprehensive Cancer Center in Washington, D.C., told CURE® previously. Their presence is not associated with a history of smoking, and ALK-positive cancers have a high likelihood of spreading to the brain.

, had an intracranial response rate of 64% among patients who had brain metastases at baseline, versus 21% of patients treated with Xalkori.

“In this randomized clinical trial, [Ensacove] showed superior systemic and intracranial efficacy compared with [Xalkori] and an overall favorable safety profile that is distinct from that of other agents in this class,” researchers stated.

Ensacove (ensartinib) has received FDA approval for treating adults with ALK-positive locally advanced or metastatic NSCLC who have not previously used an ALK-inhibitor. The phase 3 eXALT3 trial demonstrated Ensacove's efficacy, showing a significant improvement in progression-free survival compared to Xalkori (crizotinib), with median PFS times of 25.8 months versus 12.7 months. Despite this, no significant difference in overall survival was observed. Common side effects include rash, musculoskeletal pain, and fatigue. The recommended dosage is 225 mg orally daily.

The Food and Drug Administration has approved Ensacove for patients with ALK-positive locally advanced or metastatic non-small cell lung cancer who have not previously received an ALK-inhibitor.

Spencer Feldman

FDA Approves Braftovi Plus Erbitux and Chemo for Metastatic Colorectal Cancer Subset

UGN-102 May Improve Quality of Life Versus Surgery in Bladder Cancer

What is Follicular Lymphoma and Why Are Better Treatments Needed?

FDA Approves Ensacove for ALK-Positive NSCLC

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