Oncology – Skin
RCT: Nivolumab Plus Ipilimumab Shows Sustained 10-Year Survival Benefit in Advanced Melanoma
18 Sep, 2024 | 15:06h | UTCBackground: Advanced melanoma historically had a poor prognosis, with median survival under 12 months before 2011. The advent of immune checkpoint inhibitors like nivolumab (anti–PD-1) and ipilimumab (anti–CTLA-4) has significantly improved outcomes. Previous results from the CheckMate 067 trial showed longer overall survival with nivolumab plus ipilimumab or nivolumab alone compared to ipilimumab alone. As patients now live beyond 7.5 years, longer-term data are needed to address new clinical questions about survival and disease progression.
Objective: To assess the final 10-year outcomes of overall survival, melanoma-specific survival, and response durability in patients with advanced melanoma treated with nivolumab plus ipilimumab, nivolumab monotherapy, or ipilimumab monotherapy.
Methods: In the phase 3 CheckMate 067 trial, 945 patients with untreated, unresectable stage III or IV melanoma were randomized 1:1:1 to receive:
- Nivolumab plus ipilimumab: Nivolumab (1 mg/kg) and ipilimumab (3 mg/kg) every 3 weeks for four doses, then nivolumab (3 mg/kg) every 2 weeks.
- Nivolumab monotherapy: Nivolumab (3 mg/kg) every 2 weeks plus placebo.
- Ipilimumab monotherapy: Ipilimumab (3 mg/kg) every 3 weeks for four doses plus placebo.
Treatment continued until disease progression, unacceptable toxicity, or withdrawal of consent. Randomization was stratified by BRAF mutation status, metastasis stage, and PD-L1 expression. Primary endpoints were overall survival and progression-free survival; secondary endpoints included objective response rates and subgroup analyses.
Results: After 10 years, median overall survival was:
- 71.9 months with nivolumab plus ipilimumab,
- 36.9 months with nivolumab,
- 19.9 months with ipilimumab.
Hazard ratios for death were 0.53 (95% CI, 0.44–0.65; P<0.001) for nivolumab plus ipilimumab vs. ipilimumab, and 0.63 (95% CI, 0.52–0.76; P<0.001) for nivolumab vs. ipilimumab. Ten-year overall survival rates were 43% with combination therapy, 37% with nivolumab, and 19% with ipilimumab. Median melanoma-specific survival was not reached (>120 months) with combination therapy (37% alive at study end), 49.4 months with nivolumab, and 21.9 months with ipilimumab. Among patients alive and progression-free at 3 years, 10-year melanoma-specific survival was 96% with combination therapy, 97% with nivolumab, and 88% with ipilimumab. No new safety signals were observed over the extended follow-up.
Conclusions: Nivolumab plus ipilimumab demonstrated a sustained 10-year survival benefit over ipilimumab monotherapy in advanced melanoma. Nivolumab monotherapy also improved survival compared to ipilimumab, though the combination provided the greatest benefit.
Implications for Practice: These 10-year results support nivolumab plus ipilimumab as a preferred first-line treatment for advanced melanoma, offering potential for long-term survival and possible cure. Clinicians should balance improved efficacy against higher adverse event rates with combination therapy and monitor patients accordingly.
Study Strengths and Limitations: Strengths include the large, randomized, multicenter design and extended follow-up, providing robust survival data. Limitations include the trial not being powered for formal comparison between combination and monotherapy, and potential confounding from subsequent therapies on long-term outcomes.
Future Research: Further studies should aim to identify biomarkers predicting long-term response, optimize patient selection for combination therapy, and develop treatments for patients unresponsive to current immune checkpoint inhibitors.
European consensus-based interdisciplinary guideline for invasive cutaneous squamous cell carcinoma
1 Aug, 2023 | 14:24h | UTCPart 1: Diagnostics and prevention – European Journal of Cancer
Part 2: Treatment – European Journal of Cancer
Phase 2 Trial | Nivolumab shows promise as adjuvant therapy in completely resected Merkel cell carcinoma
20 Jul, 2023 | 11:02h | UTCAdjuvant immunotherapy with nivolumab versus observation in completely resected Merkel cell carcinoma (ADMEC-O): disease-free survival results from a randomised, open-label, phase 2 trial – The Lancet (link to abstract – $ for full-text)
RCT | Microdosed incisional clindamycin reduces infection rate in skin cancer surgery
30 May, 2023 | 12:03h | UTCEffect of Microdoses of Incisional Antibiotics on the Rate of Surgical Site Infections in Skin Cancer Surgery: A Randomized Clinical Trial – JAMA Surgery (link to abstract – $ for full-text)
See also: Visual Abstract
Commentary: Microdosed Incisional Clindamycin Cuts SSI After Skin Cancer Surgery – HealthDay
Cohort Study | 5-mm margins may be adequate for T1a melanoma excision near critical structures
16 May, 2023 | 14:40h | UTCAssociation of Excision Margin Size With Local Recurrence and Survival in Patients With T1a Melanoma at Critical Structures – JAMA Dermatology (link to abstract – $ for full-text)
Commentary: Melanoma Excisions with 5 Millimeter Margins Linked to Less Risk of Local Recurrence – HCP Live
Commentary on Twitter
Study on thin melanomas (T1a) near critical anatomic sites such as the head and face showed that 5-mm surgical margins may be safe for patients and decrease reconstructive surgery and potential adverse, including scarring and mental issues. https://t.co/Mw7Ub4xMVX
— JAMA Dermatology (@JAMADerm) April 12, 2023
Clinical Trial Update | Nivolumab plus Relatlimab for advanced melanoma fail to reach OS threshold despite PFS improvement
25 Apr, 2023 | 14:25h | UTCOverall Survival and Response with Nivolumab and Relatlimab in Advanced Melanoma – NEJM Evidence
Original Study: Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma – New England Journal of Medicine
Commentary on Twitter
Original Article: “Overall Survival and Response with Nivolumab and Relatlimab in Advanced Melanoma,” by Georgina V. Long, MD, PhD, et al. https://t.co/g5N1AYQV1I#OncoAlert #Melanoma
— NEJM Evidence (@NEJMEvidence) April 19, 2023
USPSTF Statement | There is insufficient evidence to guide skin cancer screening recommendations
24 Apr, 2023 | 14:07h | UTCScreening for Skin Cancer: US Preventive Services Task Force Recommendation Statement – JAMA
Evidence Report: Skin Cancer Screening: Updated Evidence Report and Systematic Review for the US Preventive Services Task Force – JAMA
Editorials:
Patient Page: Screening and Prevention of Skin Cancer – JAMA
Author Interview: USPSTF Recommendation: Screening for Skin Cancer – JAMA
Commentary on Twitter
2023 Recommendation Statement from the USPSTF concludes that the current evidence is insufficient to assess the balance of benefits and harms of visual skin examination by a clinician to screen for #skincancer in adolescents and adults (I statement). https://t.co/WB6VN2r1Nv
— JAMA (@JAMA_current) April 18, 2023
S1-guideline cutaneous and subcutaneous leiomyosarcoma
4 Apr, 2023 | 13:37h | UTCS1-guideline cutaneous and subcutaneous leiomyosarcoma – Journal of the German Dermatology Society
Guideline | Merkel cell carcinoma
23 Mar, 2023 | 12:48h | UTC
Suggested guidelines for the treatment of mycosis fungoides in countries with limited resources
21 Mar, 2023 | 13:29h | UTC
Guidelines for the management of people with cutaneous squamous cell carcinoma in situ (Bowen disease)
21 Mar, 2023 | 13:27h | UTC
FDA issues new information on cases of squamous cell carcinoma and lymphomas around breast implants
16 Mar, 2023 | 13:28h | UTCSummary: The US Food and Drug Administration (FDA) has provided an update on reports of squamous cell carcinoma (SCC) in the scar tissue (capsule) that forms around breast implants. The FDA is aware of 19 cases of SCC in the capsule around the breast implant from published literature, including 3 reports of deaths from the disease.
While the FDA continues to believe that occurrences of SCC in the capsule around the breast implant may be rare, the cause, incidence, and risk factors remain unknown. Health care providers and people who have or are considering breast implants should be aware that cases of SCC and various lymphomas in the capsule around the breast implant have been reported to the FDA and in the literature.
The FDA continues to ask health care providers and people with breast implants to report cases of SCC, lymphomas, or any other cancers around breast implants.
FDA Safety Communication: Reports of Squamous Cell Carcinoma (SCC) in the Capsule Around Breast Implants – FDA Safety Communication – U.S. Food & Drug Administration
Related:
FDA Report: 660 Cases of Breast Implant-Associated Anaplastic Large Cell Lymphoma
Study: Long-term Outcomes of Silicone Breast Implants
Phase 2 RCT | Neoadjuvant–adjuvant pembrolizumab improves event-free survival vs. adjuvant-only therapy in advanced melanoma
6 Mar, 2023 | 14:11h | UTCSummary:
This phase 2 clinical trial evaluated whether giving pembrolizumab before and after surgery (neoadjuvant-adjuvant therapy) would increase event-free survival in patients with resectable stage III or IV melanoma, compared to adjuvant therapy alone. The trial involved 313 patients, with 154 in the neoadjuvant-adjuvant group and 159 in the adjuvant-only group.
At a median follow-up of 14.7 months, the neoadjuvant-adjuvant group had significantly longer event-free survival than the adjuvant-only group, with similar rates of adverse events between groups, suggesting that pembrolizumab given both before and after surgery may be an effective treatment option for these patients.
Article: Neoadjuvant–Adjuvant or Adjuvant-Only Pembrolizumab in Advanced Melanoma – New England Journal of Medicine (link to abstract – $ for full-text)
News Release: Neoadjuvant immunotherapy improves outlook in high-risk melanoma – MD Anderson Cancer Center
Commentary on Twitter
Patients who received 3 doses of pembrolizumab before surgery and 15 doses after surgery had significantly longer event-free survival than those who received adjuvant-only therapy with 18 doses after surgery. https://t.co/qmMPV4gvSj#SkinCancer pic.twitter.com/69TDuyPAg7
— NEJM (@NEJM) March 4, 2023
RCT | Oral nicotinamide does not reduce skin cancer incidence in organ-transplant recipients
6 Mar, 2023 | 14:07h | UTCSummary:
This article discusses a phase 3 clinical trial investigating whether oral nicotinamide (vitamin B3) effectively prevents skin cancer in organ transplant recipients.
The study enrolled 158 participants who had at least two keratinocyte cancers in the past five years, with 79 assigned to the nicotinamide group and 79 to the placebo group.
After 12 months, the two groups had no significant differences in the number of squamous-cell and basal-cell carcinomas, or actinic keratoses. Adverse events and changes in blood or urine laboratory variables were also similar in the two groups.
Article: Nicotinamide for Skin-Cancer Chemoprevention in Transplant Recipients – New England Journal of Medicine (link to abstract – $ for full-text)
Related Study: A Phase 3 Randomized Trial of Nicotinamide for Skin-Cancer Chemoprevention – New England Journal of Medicine
SR | Neoadjuvant treatment for stage III and IV cutaneous melanoma
3 Mar, 2023 | 13:32h | UTCNeoadjuvant treatment for stage III and IV cutaneous melanoma – Cochrane Library
Consensus Paper | Revision of classification system for reporting on skin biopsies of melanocytic lesions
15 Jan, 2023 | 20:17h | UTCCommentaries:
MPATH-Dx Version 2.0 Simplifies Classification of Melanoma – HealthDay
Commentary on Twitter
American and international #dermatopathologists revise Melanocytic Pathology Assessment Tool and Hierarchy for Diagnosis schema. MPATH-Dx V2.0 improves standardized diagnostic reporting and patient management of #melanoma. https://t.co/G0fluzq5fs
— JAMA Network Open (@JAMANetworkOpen) January 12, 2023
RCT | Tumor-infiltrating lymphocyte therapy vs. Ipilimumab in advanced melanoma.
8 Dec, 2022 | 12:51h | UTCTumor-Infiltrating Lymphocyte Therapy or Ipilimumab in Advanced Melanoma – New England Journal of Medicine (link to abstract – $ for full-text)
Commentary: Patient’s own immune cells effective as living medicine for melanoma – Netherlands Cancer Institute
Skin cancer in solid organ transplant recipients: a review for the non-dermatologist.
27 Nov, 2022 | 22:02h | UTC
Single-arm P2 study | Neoadjuvant relatlimab and nivolumab in resectable melanoma.
8 Nov, 2022 | 12:11h | UTCNeoadjuvant relatlimab and nivolumab in resectable melanoma – Nature
News Release: Neoadjuvant immunotherapy with relatlimab and nivolumab is safe and effective in stage III melanoma – MD Anderson News Release
Commentary on Twitter
In a phase II trial of neoadjuvant & adjuvant nivolumab+relatlimab in 30 pts with stage III or oligometastatic stage IV melanoma, the pCR rate was 57%, with a 70% pRR; 1- & 2-yr RFS was 100% & 92% vs 88% & 55% for pts with vs without any path. response: https://t.co/2ypNeUTpwb
— NatureRevClinOncol (@NatRevClinOncol) November 1, 2022
RCT | Dabrafenib and Trametinib vs. Nivolumab and Ipilimumab for patients with advanced BRAF-mutant melanoma.
1 Nov, 2022 | 12:06h | UTCCommentary: Treatment Sequence Studied for Advanced BRAF-Mutant Melanoma – HealthDay
RCT | Adjuvant Nivolumab plus Ipilimumab vs. Nivolumab alone in patients with resected Stage IIIB-D or Stage IV melanoma.
30 Sep, 2022 | 12:33h | UTC
Phase 2 RCT | Combined nivolumab and ipilimumab with or without stereotactic body radiation therapy for advanced Merkel cell carcinoma.
19 Sep, 2022 | 12:32h | UTCCombined nivolumab and ipilimumab with or without stereotactic body radiation therapy for advanced Merkel cell carcinoma: a randomised, open label, phase 2 trial – The Lancet (free registration required for full-text)
Phase 2 RCT | Sequencing of Ipilimumab plus Nivolumab and Encorafenib plus Binimetinib for untreated BRAF-mutated metastatic melanoma.
14 Sep, 2022 | 13:01h | UTCSequencing of Ipilimumab Plus Nivolumab and Encorafenib Plus Binimetinib for Untreated BRAF-Mutated Metastatic Melanoma (SECOMBIT): A Randomized, Three-Arm, Open-Label Phase II Trial – Journal of Clinical Oncology (link to abstract – $ for full-text)
Commentary on Twitter
Data from the phase II SECOMBIT trial of treatment sequencing for BRAF-mutant metastatic melanoma suggests that nivo+ipi followed by encorafenib + binimetinib results in better OS than the reverse sequence, although with a greater risk of grade 3-4 AEs: https://t.co/9jC2oMI4Az
— NatureRevClinOncol (@NatRevClinOncol) September 7, 2022
Phase 2 single-arm study | Neoadjuvant Cemiplimab for stage II to IV cutaneous squamous-cell carcinoma.
13 Sep, 2022 | 13:11h | UTCNeoadjuvant Cemiplimab for Stage II to IV Cutaneous Squamous-Cell Carcinoma – New England Journal of Medicine (link to abstract – $ for full-text)
Commentary: Neoadjuvant Cemiplimab Induces Promising Pathologic Complete Response in CSCC – Cancer Network
Commentary on Twitter
A phase 2, multicenter study showed that four doses of neoadjuvant cemiplimab (anti–PD-1 antibody) led to a pathological complete response in 51% of patients with locally advanced cutaneous squamous-cell carcinoma. #ESMO22 https://t.co/NbICkb5kLM pic.twitter.com/a67fgxKBLy
— NEJM (@NEJM) September 12, 2022
RCT | Five-year analysis of adjuvant Pembrolizumab or placebo in stage III melanoma.
13 Sep, 2022 | 13:03h | UTCFive-Year Analysis of Adjuvant Pembrolizumab or Placebo in Stage III Melanoma – NEJM Evidence