Thursday, May 3, 2018

Stage III melanoma ~ 3 interesting reports:


When I was diagnosed with Stage III melanoma in 2003, I had affected bits and pieces surgically  removed, but there wasn't much else I could do - nothing that was effective anyway.  Thank goodness, the life of a Stage III melanoma patient is different now that viable, effective adjuvant treatments (Here's just a "few" posts on that topic: Adjuvant treatments in melanoma ) are available!!!  Or....are they?????????

Disparities of Immunotherapy Utilization in Patients with Stage III Cutaneous Melanoma: A National Perspective.  Al-Qurayshi, Crowther, Hamner, et al. Anticancer Res. 2018 May.
Immunotherapy combined with surgery is associated with better survival than surgery alone in patients with advanced melanoma. This study examined the utilization of immunotherapy in relation to population characteristics and the associated survival benefit.  This was a retrospective cohort study utilizing the US National Cancer Database. The study population included 6,165 adult patients (greater than/= to18 years) with stage III cutaneous melanoma (median follow-up=32 months).  A total of 1,854 patients underwent immunotherapy in addition to surgery, which was associated with a survival benefit over surgery alone. Older age, presence of comorbidities, Medicaid/Medicare insurance, and living in a community with lower average education level were associated with less immunotherapy utilization. No statistically significant racial disparity in immunotherapy usage was found.  Compared to other demographic factors, insurance status was associated with the greatest disparities in immunotherapy utilization and mortality for patients who underwent surgery for advanced melanoma.

Does this not explain why I am so pissed off??  Does this clarify my hatred of insurance companies?  Does this not elucidate ONE of the reasons I continue to yell and scream????  Health care is a human right...NOT a privilege!!!!!!!!!!  Okay...slow deep cleansing breaths....

Now, there's this ~

Adjuvant Pembrolizumab versus Placebo in Resected Stage III Melanoma. Eggermont, Blank, Mandal, et al. N Engl J Med. 2018 Apr 15. 

The programmed death 1 (PD-1) inhibitor pembrolizumab has been found to prolong progression-free and overall survival among patients with advanced melanoma. We conducted a phase 3 double-blind trial to evaluate pembrolizumab as adjuvant therapy in patients with resected, high-risk stage III melanoma. 

Patients with completely resected stage III melanoma were randomly assigned (with stratification according to cancer stage and geographic region) to receive 200 mg of pembrolizumab (514 patients) or placebo (505 patients) intravenously every 3 weeks for a total of 18 doses (approximately 1 year) or until disease recurrence or unacceptable toxic effects occurred. Recurrence-free survival in the overall intention-to-treat population and in the subgroup of patients with cancer that was positive for the PD-1 ligand (PD-L1) were the primary end points. Safety was also evaluated.

At a median follow-up of 15 months, pembrolizumab was associated with significantly longer recurrence-free survival than placebo in the overall intention-to-treat population (1-year rate of recurrence-free survival, 75.4% vs. 61.0%) and in the subgroup of 853 patients with PD-L1-positive tumors (1-year rate of recurrence-free survival, 77.1% in the pembrolizumab group and 62.6% in the placebo group). Adverse events of grades 3 to 5 that were related to the trial regimen were reported in 14.7% of the patients in the pembrolizumab group and in 3.4% of patients in the placebo group. There was one treatment-related death due to myositis in the pembrolizumab group. 

As adjuvant therapy for high-risk stage III melanoma, 200 mg of pembrolizumab administered every 3 weeks for up to 1 year resulted in significantly longer recurrence-free survival than placebo, with no new toxic effects identified.

THIS is one of THOSE reports!  You know the type.  The ones that take a good deal of time, effort, and money to tell us that:  Obesity is found in children who ingest more calories and get less exercise!  OR:  Teen depression is more frequent in children who have fewer friends!  So, not surprisingly...folks in this study who were given anti-PD-1 (in this instance it was pembrolizumab/Keytruda....we have similar reports for nivolumab/Opdivo...) did better than folks who were given placebo!  Well, duh!!!  Perhaps the most important point made in this study is that folks who were PD-L1 positive had a recurrence free survival at 1 year of 77% when treated with pembro. While the overall RFS at 1 year for those treated with pembro, no matter PD-L1 status, was basically the same at 75%.  This could be better broken down and might actually make the study worthwhile (and maybe it is in the whole article) as the overall pembro responders obviously included both PD-L1 positive and PD-L1 negative patients.  BUT...even with this limited data...it is clear that anti-PD-1 worked in some ratties whose tumors were PD-L1 positive and in some whose tumors were not!!!

Now, this...

Surveillance imaging with FDG-PET/CT in the post-operative follow-up of stage 3 melanoma. Lewin, Sayers, Kee, et al. Ann Oncol. 2018 Apr 12.

As early detection of recurrent melanoma maximizes treatment options, patients usually undergo post-operative imaging surveillance, increasingly with FDG-PET/CT (PET). To assess this, we evaluated stage 3 melanoma patients who underwent prospectively applied and sub-stage-specific schedules of PET surveillance.

From 2009, patients with stage 3 melanoma routinely underwent PET +/- MRI brain scans via defined schedules based on sub-stage-specific relapse probabilities. Data were collected regarding patient characteristics and outcomes. Contingency analyses were performed of imaging outcomes.

170 patients (stage 3A: 34; 3B: 93; 3C: 43) underwent radiological surveillance. Relapses were identified in 65 (38%) patients, of which 45 (69%) were asymptomatic. False-positive imaging findings occurred in 7%, and 6% had treatable second (non-melanoma) malignancies. Positive predictive values (PPV) of individual scans were 56% - 83%. Negative scans had predictive values of 89% - 96% for true non-recurrence (negative predictive values (NPV)) until the next scan. A negative PET at 18 months had NPVs of 80% - 84% for true non-recurrence at any time in the 47-month (median) follow-up period. Sensitivity and specificity of the overall approach of sub-stage-specific PET surveillance were 70% and 87%, respectively. Of relapsed patients, 33 (52%) underwent potentially curative resection and 10 (16%) remained disease-free after 24 months (median).

Application of sub-stage-specific PET in stage 3 melanoma enables asymptomatic detection of most recurrences, has high NPVs that may provide patient reassurance, and is associated with a high rate of detection of resectable and potentially curable disease at relapse.

Sorry, but again, Well, Duh!!!!  Stage III patients who were scanned, had recurrences found early, even when asymptomatic and therefore had "potentially curable disease".  Yet, Stage III patients (and yes...even many of us Stage IV peeps) have to fight tooth and toenail to have needed scans done and paid for by our insurance plans.  Yes, you can bet I've yelled about this as well:  The need for scans and appropriate follow-up!  The first two posts are incredibly pertinent as they include excerpts written by Rev. Carol Clark Taylor, formerly of the blog "Attitude of Gratitude", and now simply "The Queen of Melanoma", to whom we all give unending  thanks...for her grace, fortitude and the incredible advocacy she has maintained for years for all of us!!!  

Despite my current frustrations with problems in the "system" and management of melanoma generally, we have come a LOOOOOONG way, baby!  In 2003, I couldn't even fuss about these things because they didn't exist!!!  Today, THEY DO!!!  Now, we must to work to find even better treatment and follow-up options and make sure they are a reality for ALL of those who need them!!! - love, c

2 comments:

  1. I know this was from a few months ago, but I'm feeling this today. Husband just had follow-up PET/CT 1 month after completing a year of Opdivo (and 2 months after last scan). Earlier than insurance would have liked (and moved up to happen earlier than originally scheduled) but he has another growing hot spot in a lymph node near the site of the original metastasis and now we know before it is too big/spread elsewhere! Surgical consult tomorrow.

    Thanks so much for writing this--super helpful as a resource on studies and as a source of crafting fun (I'm a knitter, spinner, needle felter and have taken up sewing in the last year).

    ReplyDelete
    Replies
    1. Sorry your husband may be dealing with something new. But hopefully, since it was found early, you can find a good solution if need be. I wish you both my best.

      Delete