Sunday, February 16, 2020

Five year survival reports in melanoma after various targeted and immunotherapies

Five years.  I think every doc or researchers who touts "5 year survival" as the cat's meow really needs to think about how that would feel if applied to their life.  Now, when you are coming from a prognosis of "6 months to live" - a sentence once levied directly at me personally - five years to live certainly has a better ring to it.  Still, it is pretty sucky to have to look at five year survival as something to cheer about. But, in the crazy land that is melanoma - we'll take it.

From as early as 2016 there was this report on nivolumab (Opdivo) in advanced heavily pre-treated melanoma patients:  Nivolumab Shows Impressive OS in melanoma

This report from 2018 looked at the survival of patients on targeted therapy:  Long term outcomes with Dabrafenib/Trametinib (BRAF/MEK combo)

This abstract from last year examined survival data with the ipi/nivo combo:  Ipi/Nivo combo 5 year overall survival report for peeps with advanced melanoma!

The Keynote-001 study has put out data many times.  This link includes an abstract from Jan 2019 and links to previously published data:  KEYNOTE-001: Melanoma patients treated with Pembrolizumab (Keytruda) - 5 year survival outcomes

This report was published in April of last year:

Five-year survival outcomes for patients with advanced melanoma treated with pembrolizumab in KEYNOTE-001.  Hamid, Robert, Daud, et al.  Ann Oncol. 2019 Apr;30

Pembrolizumab demonstrated robust antitumor activity and safety in the phase Ib KEYNOTE-001 study of advanced melanoma. Five-year outcomes in all patients and treatment-naive patients are reported herein. Patients whose disease progressed following initial response and who received a second course of pembrolizumab were also analyzed.

Patients aged greater than/= to 18 years with previously treated or treatment-naive advanced/metastatic melanoma received pembrolizumab 2 mg/kg every 3 weeks, 10 mg/kg every 3 weeks, or 10 mg/kg every 2 weeks until disease progression, intolerable toxicity, or patient/investigator decision to withdraw. Kaplan-Meier estimates of overall survival (OS) and progression-free survival (PFS) were calculated. Objective response rate and PFS were based on immune-related response criteria by investigator assessment (data cut-off, September 1, 2017).

KEYNOTE-001 enrolled 655 patients with melanoma; median follow-up was 55 months. Estimated 5-year OS was 34% in all patients and 41% in treatment-naive patients; median OS was 23.8 months and 38.6 months, respectively. Estimated 5-year PFS rates were 21% in all patients and 29% in treatment-naive patients; median PFS was 8.3 months and 16.9 months, respectively. Median response duration was not reached; 73% of all responses and 82% of treatment-naive responses were ongoing at data cut-off; the longest response was ongoing at 66 months. Four patients [all with prior response of complete response (CR)] whose disease progressed during observation subsequently received second-course pembrolizumab. One patient each achieved CR and partial response (after data cut-off). Treatment-related AEs (TRAEs) occurred in 86% of patients and resulted in study discontinuation in 7.8%; 17% experienced grade 3/4 TRAE.

This 5-year analysis of KEYNOTE-001 represents the longest follow-up for pembrolizumab to date and confirms the durable antitumor activity and tolerability of pembrolizumab in advanced melanoma.

Then, there is this report on outcomes in melanoma patients when anti-PD-1 or ipi/nivo is combined WITH surgical removal of the lesion:

Survival Outcomes After Metastasectomy in Melanoma Patients Categorized by Response to Checkpoint Blockade.  Bello, Panageas, Hollmann, et al.  Ann Surg Oncol. 2019 Dec 17.

Checkpoint inhibitors have improved outcomes in metastatic melanoma, with 4-year overall survival (OS) of 46% for anti-PD-1 alone or 53% in combination with anti-CTLA-4. However, the median progression free survival is 6.9 and 11.5 months, respectively. Many who progress have gone on to alternative treatments, including surgery, yet the outcome of patients selected for surgery after checkpoint blockade remains unclear.

Patients who were treated with checkpoint blockade from 2003 to 2017, followed by metastasectomy, were identified from a prospectively maintained institutional melanoma database. Response to immunotherapy was assessed at the time of surgery. Patients were categorized as having responding, isolated progressing, or multiple progressing lesions.

Of the 237 total patients identified, 208 (88%) had stage IV disease, and 29 (12%) had unresectable stage III disease at the start of immunotherapy. Median OS following first resection was 21 months. Median follow-up among survivors was 23 months. Complete resection at the first operation (n = 87, 37%) was associated with improved survival compared with patients with incomplete resection (n = 150, 63%) [median OS not reached (NR) vs. 10.8 months. Patients resected for an isolated progressing or responding tumor had a longer median survival compared with those with multiple progressing lesions (NR vs. 7.8 months).

Patients selected for surgical resection following checkpoint blockade have a relatively favorable survival, especially if they had a response to immunotherapy and undergo complete resection of isolated progressing or responding disease

Melanoma sucks great big green hairy stinky wizard balls.  So do the treatments.  But knowledge is power and perhaps these reports can help shed some light for those facing tough decisions.  For what it's worth. - c


  1. I have been on Opdivo for a year, it was halted as it’s been unsuccessful. Metastatic melanoma, removed from neck and lung. The lung continues to have more7mm or so. Plan is to do targeted treatment. MRI has revealed what’s consistent with melanoma on my brain, 4mm. Scheduled for gamma knife on the brain. Very confidant with my oncologist. Question , all lung treatment is stopped, to address the brain, doctor questioned why other treatment is stopped but waiting for a reply ? Do or could they interfere ? Options on targeted are braftovi/ mektovi or tafinlar/mekinist , any thoughts on theses?

    1. I would seek systemic therapy asap. Studies show such therapy COMBINED with radiation produce the best results. Info on that and the targeted therapies you named can be found via the search bubble at the top left of the page. I wish you my best.