Melanoma Treatment: What Happens After Stable Disease?

observational-study PMID: 34571336

Quick Summary: Researchers looked at how well pembrolizumab, a cancer drug, worked for people with advanced melanoma. They found that if the drug initially stabilized the cancer, but then the cancer improved, patients had a good chance of long-term survival. However, if the cancer got worse after initially stabilizing, the outlook was not as good.

What The Research Found

This study looked at patients with advanced melanoma who were treated with pembrolizumab. The researchers wanted to know what happened to patients whose cancer initially stabilized (didn't get better or worse) after starting the drug. They found:

If the cancer later improved (shrank), patients had a good chance of long-term survival.

If the cancer got worse after initially stabilizing, the patients didn't do as well.

Study Details

Who was studied: People with advanced melanoma who participated in two clinical trials (KEYNOTE-001 and KEYNOTE-006).

How long: Researchers followed patients for up to 48 months (4 years).

What they took: Patients received pembrolizumab, an immunotherapy drug, given through an IV.

What This Means For You

If you or a loved one is being treated for advanced melanoma with pembrolizumab and the cancer stabilizes initially, don't lose hope! This study suggests that if the cancer later starts to shrink, you may still have a good chance of long-term survival. However, if the cancer starts to grow again, it's important to discuss other treatment options with your doctor.

Study Limitations

This study looked back at data from previous studies, so it wasn't specifically designed to answer these questions.

The patients in the study were not all the same, which could affect the results.

The study only looked at people who received pembrolizumab, so we don't know how other treatments might compare.

Key Findings

This post hoc analysis of the KEYNOTE-001 and KEYNOTE-006 trials found that among patients with advanced melanoma achieving stable disease (SD) at week 12 of pembrolizumab treatment, 46.7% later experienced partial or complete responses. Patients with SD followed by subsequent response had 48-month overall survival (OS) rates comparable to those with initial partial responses (72.1% vs. 75.0%). However, patients with SD at week 12 who progressed before week 24 had significantly worse survival (11.6% at 36 months). These results suggest early SD on pembrolizumab may still indicate potential for long-term survival if subsequent tumor shrinkage occurs, but progression after SD predicts poor outcomes.

Study Design

This observational study analyzed pooled data from two phase I (KEYNOTE-001) and III (KEYNOTE-006) clinical trials of pembrolizumab in advanced melanoma. Researchers included 294 patients with SD, partial response (PR), or complete response (CR) at week 12, and 241 patients with evaluable responses at week 24. The primary endpoint was 48-month OS rates stratified by response status at weeks 12/24. Follow-up duration extended up to 48 months.

Dosage & Administration

The study evaluated pembrolizumab, an anti-PD-1 immunotherapy drug, administered intravenously at 2 mg/kg every 3 weeks (KEYNOTE-006) or 10 mg/kg every 2 or 3 weeks (KEYNOTE-001). This analysis focused on response patterns regardless of dosing schedule, as the trials tested different regimens.

Results & Efficacy

Week 12 SD cohort: 46.7% (57/107) of patients initially classified as SD later achieved PR/CR.
48-month OS rates:
CR: 95.2%
PR: 73.0%
SD: 47.7%
Subsequent response after SD: Patients with SD at week 12 but later PR/CR had 72.1% OS at 48 months, similar to those maintaining PR (75.0%).
Progression after SD: Patients with SD at week 12 but progression before week 24 had 11.6% OS at 36 months (95% CI: 4.8–26.3).
Statistical significance: Differences in OS between response groups were significant (p < 0.001), though exact p-values for subgroup comparisons were not reported.

Limitations

Post hoc analysis: Not pre-specified, increasing risk of bias.
Heterogeneous population: Mixed patient characteristics (e.g., prior therapies, tumor markers) may confound outcomes.
Response assessment variability: SD categorization depends on RECIST criteria thresholds, which may not capture delayed responses.
Lack of mechanistic data: Does not explain why some SD patients later respond to therapy.
No control group: Results reflect pembrolizumab-treated patients only, limiting comparative conclusions.

Clinical Relevance

For patients with advanced melanoma treated with pembrolizumab, early SD should not be interpreted as treatment failure. Continuing therapy beyond initial SD (week 12) may yield meaningful long-term survival benefits if subsequent tumor shrinkage occurs. However, progression before week 24 in SD patients predicts poor outcomes, suggesting earlier discontinuation might be appropriate in this subgroup. These findings inform clinical decision-making by distinguishing SD subtypes with divergent prognoses.

Note: This study evaluates pembrolizumab (an immunotherapy drug), not Phosphatidylserine. The provided details do not align with a supplement/nutrition research context. Please verify the study details for Phosphatidylserine analysis.