• About
  • Masthead
  • License Content
  • Advertise
  • Submit Press Release
  • RSS/Email List
  • 2MM Podcast
  • Write for us
  • Contact Us
2 Minute Medicine
No Result
View All Result

No products in the cart.

SUBSCRIBE
  • Specialties
    • All Specialties, All Recent Reports
    • Cardiology
    • Chronic Disease
    • Dermatology
    • Emergency
    • Endocrinology
    • Gastroenterology
    • Imaging and Intervention
    • Infectious Disease
    • Nephrology
    • Neurology
    • Obstetrics
    • Oncology
    • Ophthalmology
    • Pediatrics
    • Pharma
    • Preclinical
    • Psychiatry
    • Public Health
    • Pulmonology
    • Rheumatology
    • Surgery
  • AI Roundup
  • Pharma
  • The Scan+
  • Classics™+
    • 2MM+ Online Access
    • Paperback and Ebook
  • Rewinds
  • Visual
  • Podcasts
  • Partners
    • License Content
    • Submit Press Release
    • Advertise with Us
  • Account
    • Subscribe
    • Sign-in
    • My account
2 Minute Medicine
  • Specialties
    • All Specialties, All Recent Reports
    • Cardiology
    • Chronic Disease
    • Dermatology
    • Emergency
    • Endocrinology
    • Gastroenterology
    • Imaging and Intervention
    • Infectious Disease
    • Nephrology
    • Neurology
    • Obstetrics
    • Oncology
    • Ophthalmology
    • Pediatrics
    • Pharma
    • Preclinical
    • Psychiatry
    • Public Health
    • Pulmonology
    • Rheumatology
    • Surgery
  • AI Roundup
  • Pharma
  • The Scan+
  • Classics™+
    • 2MM+ Online Access
    • Paperback and Ebook
  • Rewinds
  • Visual
  • Podcasts
  • Partners
    • License Content
    • Submit Press Release
    • Advertise with Us
  • Account
    • Subscribe
    • Sign-in
    • My account
SUBSCRIBE
2 Minute Medicine
Subscribe
Home All Specialties Oncology

First-line treatment with immune checkpoint inhibitor rather than BRAF and MEK leads to improved survival

bySze Wah Samuel ChanandDaniel Goldshtein
December 28, 2022
in Chronic Disease, Dermatology, Oncology
Reading Time: 3 mins read
0
Share on FacebookShare on Twitter

1. Starting treatment with nivolumab/ipilimumab rather than dabrafenib/trametinib resulted in an improvement in 2-year overall survival (72% vs 52%)

2. The incidence of adverse events grade 3 or higher was relatively similar across all arms, although the events themselves differed.

Evidence Rating Level: 1 (Excellent)

Study Rundown: BRAF-mutant melanoma uses the MAP kinase pathway to drive cell proliferation, and it has been shown that BRAF/MEK inhibitor combinations (such as dabrafenib/trametinib) have led to several improved outcomes. Checkpoint inhibitor immunotherapy (such as nivolumab/ipilimumab) had also been shown to be effective, but there was no consensus as to the optimal sequence of therapies for new patients. This study investigated the optimal treatment sequence between nivolumab/ipilimumab (arm A) and dabrafenib/trametinib (arm B) followed by swapping treatments for arms C (dabrafenib/trametinib) and D (nivolumab/ipilimumab) for those who had disease progression. The primary endpoint was 2-year overall survival (OS), and secondary endpoints included 3-year OS, objective response rate (ORR), duration of response (DoR), progression-free survival (PFS) and safety. 2-year OS favored starting on nivolumab/ipilimumab (71.8%) vs dabrafenib/trametinib (51.5%). This difference was considered clinically meaningful and patients on dabrafenib/trametinib were given the option to switch to nivolumab/ipilimumab without the need for disease progression. 3-year OS followed a similar pattern, 66.2% (arm A) vs 42.8% (arm B). PFS also favored nivolumab/ipilimumab followed by dabrafenib/trametinib compared with the opposite, with 11.8 months (arm A), 8.5 months (arm B), 9.9 months (arm C), and 2.9 months (arm D). ORR was similar in arms A, B, and C, but lower in D meaning nivolumab/ipilimumab appeared less effective after progression on dabrafenib/trametinib. The incidence of adverse events grade 3 or higher was relatively similar across all arms. The strengths of this study included longer follow-up time. Limitations to this study included a small sample size, and the inclusion of only healthy participants. Overall, for patients diagnosed with BRAF positive melanoma, starting therapy with nivolumab/ipilimumab followed by dabrafenib/trametinib led to improved outcomes.

Click to read the study in JCO

Relevant Reading: Long-Term Outcomes With Nivolumab Plus Ipilimumab or Nivolumab Alone Versus Ipilimumab in Patients With Advanced Melanoma

RELATED REPORTS

#VisualAbstract: Adjuvant Dabrafenib plus Trametinib Improves Outcomes in Stage III Melanoma

#VisualAbstract: Neoadjuvant Nivolumab and Ipilimumab Improve Outcomes in Resectable Stage III Melanoma

Atezolizumab, Vemurafenib, and Cobimetinib in Melanoma With CNS Metastases

In-Depth [randomized controlled trial]: This study enrolled 265 patients, who were otherwise healthy, with histologically confirmed unrespectable stage III or IV melanoma with a BRAFV600E/K mutation into a two-arm, two-step, open-label, randomized phase 3 trail. Patient were initially assigned to nivolumab/ipilimumab (arm A, 133 patients) or dabrafenib/trametinib (arm B, 132) in step 1 and then at disease progression (defined by RECISTv1.1) enrolled in step 2 with alternate therapy, dabrafenib/trametinib (arm C, 27) or nivolumab/ipilimumab (arm D, 46). Initial patient characteristics were balanced but arm B had more BRAFV600K and less BRAFV600E mutation tumors than arm A. Median follow-up time was 27.7 months. 2-year OS rate followed a biphasic curve with 71.8% (95%CI, 62.5-79.1) for patients starting in arm A and 51.5% (95%CI, 41.7-60.4) for patients starting arm B (p = 0.010). Given this difference, arm B was given the option to switch to arm D without the need for disease progression. 3-year OS followed a similar pattern, 66.2% in those starting in arm A and 42.8% in those starting in arm B. Median PFS also followed a biphasic pattern with 11.8 months (95%CI, 5.9-33.5) for arm A, 8.5 months (95%CI, 6.5-11.3) for arm B, 9.9 months (95%CI, 8.3-20.8) for arm C, and 2.9 months (95%CI, 2.6-8.9) for arm D. ORR was similar for both arms in step 1 (46% in arm A, and 43% in arm B), but showed a difference for step 2 with 47.8% (95%CI, 26.8-69.4) in arm C vs 29.6% (95%CI, 12.7-47.2) in arm D. Median DoR was longer in arm A than arm B. The incidence of adverse events grade 3 or higher was relatively similar across all arms (59.5% in arm A, 53.1% in arm B, 53.8% in arm C, and 50% in arm D), with more immune related events occurring in arms A/D and more fevers, leukopenia, and hyponatremia in arms B/C. Overall, this study found that starting therapy with nivolumab/ipilimumab compared to dabrafenib/trametinib resulted in improved outcomes for BRAF positive melanoma.

Image: PD

©2022 2 Minute Medicine, Inc. All rights reserved. No works may be reproduced without expressed written consent from 2 Minute Medicine, Inc. Inquire about licensing here. No article should be construed as medical advice and is not intended as such by the authors or by 2 Minute Medicine, Inc.

Tags: advanced melanomaBRAF-mutated melanomaimmune checkpoint inhibitors (ICI)
Previous Post

Sports betting may be associated with elevated levels of problem gambling

Next Post

Second-line immunosuppression associated with worse outcomes for immune-related adverse events in melanoma

RelatedReports

#VisualAbstract: Adjuvant Dabrafenib plus Trametinib Improves Outcomes in Stage III Melanoma
StudyGraphics

#VisualAbstract: Adjuvant Dabrafenib plus Trametinib Improves Outcomes in Stage III Melanoma

July 3, 2024
#VisualAbstract: Neoadjuvant Nivolumab and Ipilimumab Improve Outcomes in Resectable Stage III Melanoma
Chronic Disease

#VisualAbstract: Neoadjuvant Nivolumab and Ipilimumab Improve Outcomes in Resectable Stage III Melanoma

June 18, 2024
Stereotactic radiosurgery promising for patients with multiple brain metastases
Oncology

Atezolizumab, Vemurafenib, and Cobimetinib in Melanoma With CNS Metastases

October 9, 2023
#StudyGraphics: Atezolizumab in combination with vemurafenib and cobimetinib improve progression-free survival in patients with BRAFV600-advanced melanoma
StudyGraphics

#StudyGraphics: Atezolizumab in combination with vemurafenib and cobimetinib improve progression-free survival in patients with BRAFV600-advanced melanoma

April 28, 2023
Next Post
Study explores effects of daily iron supplementation in 2- to 5-year-olds

Second-line immunosuppression associated with worse outcomes for immune-related adverse events in melanoma

Shorter hospital stays after hip fracture linked to greater risk of short-term death

Hip braces may delay hip surgery for children with non-ambulatory cerebral palsy

Parents often unaware of adolescents’ suicidal thoughts

Multiple psychotherapy interventions effective in borderline personality disorder

2 Minute Medicine® is an award winning, physician-run, expert medical media company. Our content is curated, written and edited by practicing health professionals who have clinical and scientific expertise in their field of reporting. Our editorial management team is comprised of highly-trained MD physicians. Join numerous brands, companies, and hospitals who trust our licensed content.

Recent Reports

  • SGLT2 inhibitors may delay cognitive impairment in elderly patients with heart failure
  • Nerandomilast slows decline in FVC in idiopathic pulmonary fibrosis
  • Mazdutide significantly reduces weight in adults with overweight or obesity
License Content
Terms of Use | Disclaimer
Cookie Policy
Privacy Statement (EU)
Disclaimer

© 2021 2 Minute Medicine, Inc. - Physician-written medical news.

  • Specialties
    • All Specialties, All Recent Reports
    • Cardiology
    • Chronic Disease
    • Dermatology
    • Emergency
    • Endocrinology
    • Gastroenterology
    • Imaging and Intervention
    • Infectious Disease
    • Nephrology
    • Neurology
    • Obstetrics
    • Oncology
    • Ophthalmology
    • Pediatrics
    • Pharma
    • Preclinical
    • Psychiatry
    • Public Health
    • Pulmonology
    • Rheumatology
    • Surgery
  • AI Roundup
  • Pharma
  • The Scan
  • Classics™
    • 2MM+ Online Access
    • Paperback and Ebook
  • Rewinds
  • Visual
  • Podcasts
  • Partners
    • License Content
    • Submit Press Release
    • Advertise with Us
  • Account
    • Subscribe
    • Sign-in
    • My account
No Result
View All Result

© 2021 2 Minute Medicine, Inc. - Physician-written medical news.