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Medscape
08-07-2025
- Health
- Medscape
Real-World Data: Adjuvant Therapy for BRAF-Mutated Melanoma
This transcript has been edited for clarity. Hello, everybody. My name is Teresa Amaral. Welcome back to this Medscape Oncology series on melanoma. Today, we'll finalize a discussion about real-world data on adjuvant therapy in patients with BRAF -mutated melanoma. We discussed the visual comparison between immunotherapy and targeted therapy using real-world data. We also discussed the benefit in terms of relapse-free survival and distant metastasis-free survival in this adjuvant setting when we compared the two therapies, showing that visual comparison seems to show a better benefit for patients receiving targeted therapy compared to immunotherapy. We looked into the differences in terms of quality of life and the toxicity profile for both therapies. Now, we will look into the last aspect that we need to discuss with our patients, which is what we do when the patients have a relapse. Obviously, it is different whether the patients have a relapse under adjuvant therapy or off adjuvant therapy. Patients who have a recurrence under adjuvant targeted therapy seem to benefit from programmed cell death protein 1 (PD-1) therapy afterward in a similar way as patients who had PD-1 monotherapy in stage IV and were treatment naive. Patients with recurrence under adjuvant PD-1 therapy do not seem to benefit from continuing PD-1 therapy, but they might benefit from other immunotherapies, such as ipilimumab or the combination of ipilimumab plus PD-1. We have other real-world data, which we've discussed in the episodes before, on where to go in terms of immunotherapy judgment setting. Even if we have a prolongation in terms of relapse-free survival or metastasis-free survival, when we look into overall survival data from real-world studies, we don't see a benefit in either of the two cohorts, one before introducing adjuvant therapy and another after introducing adjuvant therapy. This is also something that we need to discuss with our patients when we propose adjuvant therapy. The paper I mentioned before is an indirect comparison, and of course, it needs to be read as so. There are real-world data that have been analyzed, but obviously, we cannot change the data and how they were analyzed. When we look into the relapse-free survival events, we need to consider that these events are dependent on the timing when the imaging evaluation was performed. If you have an imaging evaluation that was performed a little bit earlier, you might detect relapse-free survival earlier as compared to an imaging evaluation that was performed later. The criteria for including these studies in this analysis was the same, but inclusion criteria may vary in the different trials, which might lead to a bias. Another aspect that is important to retain from this analysis is that we included both patients with BRAF wild-type and BRAF -mutated melanoma, because we could not separate these as we didn't have access to raw data. We also included all patients despite the BRAF mutation subtype. We didn't know if the patients were BRAF V600E or K, although the majority were reported as having BRAF V600E. We also were not able to analyze the data based on the substage — so stage IIIA to IIID. We included all the patients as stage III, but not the substage. Although the median follow-up time is long, it might not be long enough to capture all the events in the adjuvant setting. We probably need an update of this work in the near future. We were unable to exclude a couple of patients that were stage IV with no evidence of disease that were included in the different publications because we didn't have access to the raw data. We didn't perform any statistical comparison because of the differences in terms of the publications that we selected. The comparison was visually performed based on the formula that I mentioned in the first episode of this series. We have some advantages from this analysis. One is the number of patients, where more than 3600 patients were included. We included analyses that started around 2018, which means that, for the majority of the patients, they would have had access to PD-1 therapies or PD-1-based therapies as in the modern era if they had progressive disease or a recurrence. We don't know if this is the case for all the patients included in the analysis. Finally, grouping all the analyses and doing this digitalization using this visual comparison is obviously, I would say, an advantage. Another advantage is the fact that we used weighted average calculations to produce these Kaplan-Meier curves, showing that there is a concordance among the different works that we selected for this analysis. In conclusion, I would say that, based on this real-world analysis, targeted therapy seems to have a better outcome when we look into relapse-free survival and distant metastasis-free survival in stage III. Targeted therapy has a different profile from immunotherapy, and this needs to be discussed with the patients, especially when we look into long-term toxicity. Also, the impact in terms of quality of life between these two therapies seems to be different, and this needs to be taken into consideration when we discuss this with our patients. With that, I'll finish this three-episode series. I look forward to your comments and to our next series together. Enjoy your day.
Medscape
09-06-2025
- Health
- Medscape
Making Sense of Melanoma Care Without OS Data
This transcript has been edited for clarity. Welcome back, everybody. My name is Teresa Amaral, and it's a pleasure as always to have you here for this melanoma series on Medscape. We will finalize this series on where we should go, and what's next in terms of immunotherapy in the adjuvant setting, by looking into the two other aspects that we need to consider when we discuss the factthat there is no overall survival benefit nor are there data on the overall survival benefit for patients treated with immunotherapy in the adjuvant setting. We discussed the first one, which was the fact that there might be some discussions or some uncertainties in terms of the reimbursement because these data are not available yet and might only be available in 2028. We also discussed the number of patients that are needed to treat to prevent a recurrence, especially when we are talking about stage II disease. As well as the fact that this might lead to some uncertainty, both from the treating physicians and the patients, when they need to decide whether they will receive adjuvant therapy or when they will offer adjuvant therapy to their patients. The final point that I would like to bring to the discussion is that this uncertainty might lead to a potential shift to using targeted therapy instead of immunotherapy in patients that have a BRAF V600 mutation. Why is this the case? We have data provided by the COMBI-AD study that investigated targeted therapy, in this case, dabrafenib and trametinib, in patients with BRAF V600–mutated melanoma. We saw that, similar to what we see in immunotherapy, there is a benefit in terms of relapse-free survival and distant metastasis-free survival. We also saw that there was no overall survival benefit for the whole population, but there was a higher benefit when we look numerically at 3, 5, and 7 years, especially for patients with BRAF V600E mutations. It came as a surprise, I would say, that patients with BRAF V600K not only didn't benefit from targeted therapy in the long run in terms of overall survival, despite having a benefit in terms of relapse-free survival, but when the overall survival analysis was conducted, we actually saw a detrimental effectfor patients with BRAF V600K when we compared the treatment with placebo. For these patients, we should not provide adjuvant therapy with targeted therapy. When we compare targeted therapy with immunotherapy in a real-world setting — and this will be the topic for our next series — we see that patients who had received target therapy might have a larger benefit when we look into relapse-free survival and distant metastasis-free survival compared with patients who received I'm only talking about patients who have a BRAF V600 mutation. Finally, some patients may prefer targeted therapies and oral therapy compared with immunotherapy that is given intravenously in the hospital. We see three points that might be associated with the absence of data on overall survival benefit for immunotherapy: the fact that there might be some reimbursement discussions that are associated with this aspect; the fact that in some cases, despite this therapy being recommended in the guidelines, there might be some uncertainty from the doctors and the patients onreceiving and on proposing this therapy; and a potential shift in the use of targeted therapy in favor of immunotherapy for patients with BRAF -mutated melanoma. If we don't have an overall survival benefit, why are we recommending this therapy? What is the benefit of having a relapse-free survival and a distant metastasis-free survival benefit? I would argue that for the patients, this is quite an important event. We have shown that diagnosis of recurrence is the aspect that most impacts the quality of life. When the patients are diagnosed with a recurrence, the quality of life decreases significantly. These data were, for example, mentioned during the COMBI-AD quality of life analysis. Obviously, the fact that the patients live longer without disease might provide them access to new therapies currently being investigated that were not available at the time they were treated with the adjuvant therapy, but might be available for them if they live longer without recurrence. In real-world data, we also see that approximately 50% of patients who are diagnosed with stage IIIB melanoma will be diagnosed with metastatic disease. Although in some cases we might be able to provide surgical resection, neoadjuvant therapy, or other local therapies, such as radiotherapy, for example, the fact is that some patients will have unresectable disease or will be diagnosed with metastatic and inoperable stage IV melanoma, which is quite important and in some cases is associated with a worse outcome.A longer time without evidence of recurrence is important and might lead to a better outcome in the long run. In conclusion, from our discussion so far, we can say that trial data are eagerly awaited, and mature trial data are necessary. In the meantime, we might be able to use real-world data to compensate for that and to analyze and maybe inform the way that we use programmed cell death protein 1 (PD-1) in the real-world setting in our daily practice. When we look into the absence of overall survival benefit, we also need to consider access in terms of therapies post-recurrence. When the patients recur, they might have access to all the approved therapies or not. This also highlights the importance of deciding the kind of control arm that we use when we design trials in the advancedsetting. Depending on the type of control arm and the access of patients to these types of clinical trials, we might influence the overall survival benefit in these cases. There is currently a dual strategy for treating patients diagnosed with stage IIIB or higher might be neoadjuvant therapy if we have macroscopically diagnosed disease, or it can be adjuvant therapy if we have a patient who has microscopic disease and therefore is not a candidate for immunotherapy in the neoadjuvant setting. We expect these patients to be around 40%, but also there will be patients diagnosed with stage IIIA and patients with stage IIB and IIC that will be candidates for adjuvant therapy. Finally, the absence of overall survival data, and also the presence of relapse-free survival and distant metastasis-free survival data associated with the toxicity profile of these therapies, are important to be discussed and are part of this shared decision in terms of the treatment that these patients can be offered at this timepoint that we're discussing. With that, I thank you for your attention and I look forward to seeing you again in the near future. Thank you.
Medscape
05-06-2025
- Health
- Medscape
Ethanol Ablation Shows Promise in Thyroid Cancer Treatment
Ethanol ablation was highly effective in treating smaller and pure cystic metastatic lymph nodes (MLNs) in patients with papillary thyroid carcinoma, but it was less effective in treating larger or solid nodes. Patients with lower disease stages at diagnosis were more likely to have a good response to ethanol ablation. METHODOLOGY: Previous studies have shown durable responses to ethanol ablation in 60%-95% of treated MLNs. Identifying patients who will benefit from this nonsurgical option is crucial to reducing the risk for complications from multiple surgeries. Researchers identified 75 patients (median age, 57 years; 57% women) with papillary thyroid carcinoma who underwent ethanol ablation for MLNs at the Norwegian Radium Hospital, Oslo, Norway, from 2007 to 2020. All patients had undergone total or subtotal thyroidectomy as primary treatment, followed by one or more sessions of 131 I ablation. I ablation. A total of 134 ethanol ablation-treated MLNs were included in the analysis: 57 lesions were located in the central neck region, whereas the remaining 77 lesions were distributed across the left and right lateral regions. Patients were followed up for a median of 119 months, with treatment response assessed through clinical examinations and ultrasound. The outcomes of ethanol ablation and the time to recurrence were evaluated. Ultrasonographic features of MLNs, history of lymph node surgery, BRAF V600E mutation status, and aggressive subtypes were evaluated as predictors of response to ethanol ablation treatment. TAKEAWAY: Ethanol ablation achieved a durable response in 98 (73%) of treated MLNs, with 49 nodes showing a lasting response after a single procedure and 49 requiring multiple treatments. Pure cystic MLNs showed a 100% response rate to ethanol ablation, which was significantly higher than that of solid or partially cystic nodes (74%; P = .039). Additionally, smaller MLNs (≤ 0.5 mL) had a higher response rate than larger lesions (77% vs 53%; P = .045). No significant difference in response was seen between patients with the BRAF V600E mutation and those without it. = .039). Additionally, smaller MLNs (≤ 0.5 mL) had a higher response rate than larger lesions (77% vs 53%; = .045). No significant difference in response was seen between patients with the mutation and those without it. Among 57 patients who attained locoregional control with no detectable disease on the neck, 44 achieved it solely through ethanol ablation. No major complications occurred following ethanol ablation, with transient postprocedure hoarseness noted in 6.7% of patients. Patients with three or more treated MLNs were more likely to need additional surgery or have persistent nodes (odds ratio [OR], 6.945; P = .017). Moreover, lower disease stages (I and II) were associated with better outcomes following ethanol ablation compared with stages III and IV (OR, 30.510; P = .005) in multivariable analysis. IN PRACTICE: 'Our results suggest that neither a positive BRAF mutation status nor an aggressive histological subtype in the primary tumor is crucial to determine if the patient will be a suitable candidate for EA [ethanol ablation],' the authors wrote. 'While surgery remains the first-line treatment, further evidence is needed to better understand any potential role of EA as an alternative to surgery in selected cases, also in surgically untreated neck regions,' they added. SOURCE: This study was led by Pål Stefan Frich, The Norwegian Radium Hospital, Oslo University Hospital in Oslo, Norway. It was published online in The Journal of Clinical Endocrinology & Metabolism . LIMITATIONS: The exclusion of many eligible patients increased the risk for selection bias, affecting the generalizability of the findings. The sample size was limited and division into small subgroups reduced the study's statistical power. The retrospective design and long follow-up periods posed a risk for information bias due to incomplete documentation. DISCLOSURES: This study was supported by grants from the Ødegaard and Frimann-Dahls foundation. The authors declared no relevant conflicts of interest.
Medscape
05-06-2025
- Business
- Medscape
Targeted Therapy Wins Big for BRAF-Mutated Metastatic CRC
The latest results from the BREAKWATER trial have confirmed encorafenib plus cetuximab with chemotherapy as the new first-line standard of care for BRAF V600E-mutant metastatic colorectal cancer (CRC), according to research presented at the American Society of Clinical Oncology (ASCO) 2025 annual meeting. At the interim analysis, encorafenib plus cetuximab with mFOLFOX6 chemotherapy doubled median overall survival compared with the current standard of care — investigators' choice of chemotherapy with or without bevacizumab. In addition, at a median follow-up of 16.8 months, the new treatment regimen led to a significant improvement in median progression-free survival of almost 6 months. This survival finding is 'unprecedented' and 'practice changing' for these patients who historically have a poor prognosis, said lead investigator and presenter Elena Élez, MD, PhD, a gastrointestinal medical oncologist at the Vall d'Hebron University Hospital in Barcelona, Italy. The study was published in The New England Journal of Medicine to coincide with Élez's presentation. BRAF mutations, which occur in up to 12% of patients with metastatic CRC, are associated with poor outcomes. In December 2024, the US Food and Drug Administration (FDA) granted accelerated approval for the BRAF inhibitor encorafenib alongside cetuximab and mFOLFOX6 for patients with metastatic CRC and a BRAF V600E mutation. This approval was based on earlier results from BREAKWATER that showed a 21% higher objective response rate and a longer duration of response with this regimen. The accelerated approval means that this regimen has already been making its way into the clinic, but 'we were all waiting for this [latest] data,' Pamela Kunz, MD, chief of Gastrointestinal Medical Oncology at Yale University in New Haven, Connecticut, told Medscape Medical News . The doubling of overall survival 'is a big deal,' she said. In the trial, patients were randomly assigned to receive either first-line encorafenib plus cetuximab with mFOLFOX6 (n = 236) or to a control group — physician's choice of either mFOLFOX6, FOLFOXIRI, or CAPOX chemotherapy (n = 243). Most patients in the control arm also received the tumor angiogenesis inhibitor bevacizumab. The broad options in the control arm speak to how heterogeneous treatment has been for BRAF V600E-mutant metastatic CRC, said study discussant Andrea Sartore-Bianchi, MD, a medical oncologist at the University of Milan, Milan, Italy. Patients in the trial had received no prior systemic therapy for metastatic disease. Investigators excluded patients with high levels of microsatellite instability because they are candidates for immunotherapy. At a median follow-up of 16.8 months, median progression-free survival was 12.8 months for the encorafenib group compared with 7.1 months for the control group (hazard ratio [HR], 0.53; P < .0001). At a median follow-up of 22 months, overall survival was 30 months in the encorafenib group compared with 15 months in the control group (HR, 0.49; P < .0001). The benefits of the combination were held up in high-risk subgroups, including in patients with liver metastases and those with metastases in three or more organs. With the use of more agents and a longer duration of treatment due to improved efficacy, there was an expected increase in toxicity with the new regimen. The rate of treatment-related grade 3/4 adverse events was 76.3% with encorafenib vs 58.5% with the control regimen. Patients receiving encorafenib also had higher rates of anemia, arthralgia, rash, and pyrexia, but there was no substantial increase in treatment discontinuation. BREAKWATER also included an encorafenib plus cetuximab arm without chemotherapy, but enrollment was stopped early at 158 patients due to possible futility. Still, these patients had as good or numerically better outcomes than the control group, which means the drug combination alone is a valid option for those unable to tolerate chemotherapy, said Élez. 'The results are striking,' said Sartore-Bianchi in his discussion. 'Now that we have the big picture' from BREAKWATER, the combination should be considered the first-line standard of care. Mark A. Lewis, MD, a gastrointestinal medical oncologist at Intermountain Healthcare in Murray, Utah, explained that what usually happens in metastatic CRC is that people are treated with chemotherapy for a bit before oncologists notice the tumor is behaving more aggressively than expected and order a BRAF test. This delay is now 'completely unacceptable,' he told Medscape Medical News . The takeaway from BREAKWATER is that testing must come sooner. To help with BRAF testing, the FDA approved the Qiagen therascreen BRAF V600E RGQ polymerase chain reaction kit. 'As soon as you know patients are BRAF -mutated, you need to play your entire hand' because it will double survival,' said Lewis. 'This absolutely validates a biomarker-informed approach to colon cancer,' similar to what we have in breast cancer. BREAKWATER was funded primarily by Pfizer, maker of encorafenib, with support from Eli Lilly and Merck, who jointly market cetuximab. Élez reported numerous ties to the companies, including research grants, travel funding, honoraria, and/or consultant work. Lewis, Kunz, and Sartore-Bianchi had no relationships with the firms.
Yahoo
30-05-2025
- Business
- Yahoo
Pfizer Reports Survival Gains In Colorectal Cancer Study, Combo Therapy Cuts Death Risk By Over 50%
Pfizer Inc. (NYSE:PFE) on Friday released data from Phase 3 BREAKWATER trial evaluating BRAFTOVI (encorafenib) in combination with cetuximab (marketed as ERBITUX) and mFOLFOX6 (fluorouracil, leucovorin, and oxaliplatin) for metastatic colorectal cancer (mCRC) with a BRAF V600E mutation. The study showed statistically significant and clinically meaningful survival results. The data will be presented at the 2025 American Society of Clinical Oncology (ASCO) Annual Meeting and published in the New England Journal of a second interim analysis of overall survival (OS), a key secondary endpoint, the BRAFTOVI combination regimen reduced the risk of death by 51% compared to standard-of-care chemotherapy with or without bevacizumab (Hazard Ratio [HR] 0.49). Median OS was 30.3 months with BRAFTOVI in combination with cetuximab and mFOLFOX6 compared to 15.1 months with chemotherapy with or without bevacizumab. In the primary analysis of progression-free survival (PFS), the BRAFTOVI combination regimen reduced the risk of disease progression or death by 47% compared to standard-of-care chemotherapy with or without bevacizumab (HR 0.53) as assessed by blinded independent central review (BICR). Median PFS was 12.8 months with the BRAFTOVI combination regimen compared to 7.1 months. The updated objective response rate (ORR) by BICR confirmed the improvement previously observed with the BRAFTOVI combination regimen compared to patients receiving chemotherapy with or without bevacizumab. The prior primary analysis also maintained the estimated median duration of response and median time to response. The BRAFTOVI combination regimen received accelerated approval by the U.S. Food and Drug Administration (FDA) in December 2024 for patients with BRAF V600E -mutant mCRC based on a clinically meaningful and statistically significant improvement in confirmed ORR in treatment-naïve patients, the study's other dual primary endpoint. Continued approval for this indication is contingent upon verification of clinical benefit. The BREAKWATER survival data are being discussed with the U.S. FDA to support potential conversion to full approval in 2025. Price Action: PFE stock is up 0.51% at $23.57 at the last check on Friday. Read Next:Photo via Shutterstock Up Next: Transform your trading with Benzinga Edge's one-of-a-kind market trade ideas and tools. Click now to access unique insights that can set you ahead in today's competitive market. Get the latest stock analysis from Benzinga? PFIZER (PFE): Free Stock Analysis Report This article Pfizer Reports Survival Gains In Colorectal Cancer Study, Combo Therapy Cuts Death Risk By Over 50% originally appeared on © 2025 Benzinga does not provide investment advice. All rights reserved. 登入存取你的投資組合
