Summary

In this conversation, James Larkin and Sapna Patel discuss the PRADO study, which focuses on neoadjuvant therapy for melanoma. The study explores the use of personalized response-driven approaches to treatment, based on the patient's response to combination immunotherapy. The study found that patients with a major pathological response had a low rate of recurrence in the first two years, suggesting a favorable outcome. However, there were still some patients who experienced recurrence, particularly those with multiple clinically positive lymph nodes. The discussion also touches on the challenges of defining and categorizing pathological response and the importance of accurate sampling and analysis.

Keywords

PRADO, neoadjuvant therapy, melanoma, personalized response-driven approach, major pathological response, recurrence, lymph nodes, sampling, analysis

Takeaways

Sound Bites

"Patients with a major pathological response had an excellent response."

"Patients with multiple clinically positive lymph nodes may require additional surgery."

"The definition of pathological response is not uniform across tumor types."

Chapters

00:00 Introduction and Favorite Recording Artists

02:30 Background and Importance of the Prado Study

07:00 Categorizing Pathological Responses and Cherry Picking Lymph Nodes

08:38 Hypotheses and Outcomes for Major Pathologic Response

11:42 Setting Cutoffs and the Role of Sampling in Pathology

23:42 Global Impact of the PRADO Study and the Need for Adjuvant Therapy

Summary

In this conversation, James Larkin and Sapna Patel discuss neoadjuvant treatment in melanoma. They start by talking about the best films they've seen in the last five years, then move on to the background and rationale behind neoadjuvant therapy. They discuss the use of BRAF targeted therapy and its limitations, as well as the effectiveness of immunotherapy in the neoadjuvant setting. They also touch on the importance of biomarkers and the potential for reducing surgery and adjuvant therapy in the future. The conversation highlights the OPACIN neo study and its findings, as well as the need for further research in this area.

Keywords

neoadjuvant treatment, melanoma, BRAF targeted therapy, immunotherapy, biomarkers, surgery, adjuvant therapy, OPACIN neo

Takeaways

Sound Bites

"The education you get while the tumor is clearly visible is stronger than the education the immune system would get if you removed it and then it was fighting microscopic cancer."

"Immunotherapy gives you immunological memory that continues after you take the drug away."

"The patients who got neoadjuvant therapy had a more amplified and a more diverse immune system."

Chapters

00:00 Introduction and Film Discussion

02:30 The Background of Neoadjuvant Treatment

03:50 Neoadjuvant Treatment with BRAF Targeted Therapy

07:26 The Promise of Immunotherapy in Neoadjuvant Treatment

08:33 The OPACINeo Study and Biomarkers

19:03 Conclusion

Summary

Birth order and bad second languages and Bolivia. In this episode of Melanoma Matters, hosts Sapna Patel and James Larkin discuss the Checkmate 915 trial, a significant study in the adjuvant treatment of melanoma. They explore the trial's design, the implications of IPI dosing, and the balance between efficacy and toxicity. The conversation emphasizes the importance of understanding negative studies in clinical research and the need for careful consideration in trial design, particularly in the adjuvant setting.

Keywords

Checkmate 915, melanoma, adjuvant therapy, IPI dosing, trial design, toxicity, efficacy, negative studies, immunotherapy, clinical trials

Takeaways

Checkmate 915 was a large adjuvant trial in melanoma.

The trial compared Nivolumab monotherapy to Nivolumab with low-dose IPI.

There was no improvement in relapse-free survival with the addition of IPI.

Toxicity was higher in the IPI-containing arm, as expected.

The dosing of IPI in Checkmate 915 was significantly lower than in metastatic settings.

Understanding the trade-off between efficacy and toxicity is crucial in adjuvant therapy.

Negative studies are important for learning and future trial designs.

The design of Checkmate 915 was pragmatic given the context of adjuvant treatment.

Future research may benefit from exploring neoadjuvant models.

The conversation highlights the need for more discussions on negative trials.

Titles

Checkmate 915: What Went Wrong?

Understanding Checkmate 915: A Deep Dive

Sound Bites

"This was an important large study in our field."

"The addition of this low dose IPI regimen did not improve relapse free survival."

"We need to try and think more and talk more about why studies are negative."

Chapters

00:00 Introduction and Quick Fire Questions

02:50 Discussion of Checkmate 915 Study

11:02 The Dosing Dilemma: Ipilimumab in the Adjuvant Setting

15:41 Takeaways from Checkmate 915 Study

Summary

In this episode of Melanoma Matters, hosts Sapna Patel and James Larkin have a disastrous quickfire discussing their would-be porn star names and eventually move on to the Checkmate 76K study, which evaluates the efficacy of Nivolumab in adjuvant therapy for stage 2 melanoma. They delve into the interpretation of hazard ratios, the choice between Nivolumab and Pembrolizumab, and the management of toxicities associated with these treatments. The conversation also touches on the future of subcutaneous formulations and their potential impact on patient care. Key takeaways highlight the importance of monitoring and the implications of insurance on treatment decisions.

Keywords

melanoma, adjuvant therapy, Checkmate 76K, Nivolumab, Pembrolizumab, hazard ratio, toxicity management, subcutaneous formulations

Takeaways

Checkmate 76K shows clear benefit in relapse-free survival.

Nivolumab and Pembrolizumab are both viable options.

Hazard ratios can be misinterpreted; context is crucial.

Pragmatism and reimbursement influence treatment choices.

Regular monitoring is essential for managing toxicities.

Subcutaneous formulations may improve patient convenience.

Early nephritis is a significant concern in treatment.

Insurance issues can complicate treatment decisions.

Data from Checkmate 76K aligns with Keynote 716 findings.

Patient safety should always be prioritized in therapy.

Sound Bites

"Checkmate 76K shows clear benefit in RFS."

"Nivolumab versus Pembrolizumab, both are options."

"Managing toxicities is crucial in adjuvant therapy."

Chapters

00:00 Introduction and Rapid Fire Questions

02:33 Overview of Checkmate 76K Study

05:08 Choosing between Nivolumab and Pembrolizumab

13:11 Potential of Subcutaneous Formulations

15:25 Summary and Conclusion

Summary

In this episode of Melanoma Matters, James Larkin and Sapna Patel discuss the Keynote 716 trial, focusing on the treatment of stage 2 melanoma. They explore the implications of adjuvant therapies, the significance of recurrence-free survival (RFS) and distant metastasis-free survival (DMFS), and the role of BRAF testing in managing stage 2 patients. The conversation highlights the challenges in treating early-stage melanoma and the need for accurate biomarkers to identify high-risk patients. The episode concludes with reflections on the findings of Keynote 716 and future directions in melanoma treatment.

Keywords

melanoma, Keynote 716, stage 2 melanoma, adjuvant treatment, BRAF testing, recurrence-free survival, distant metastasis-free survival, immunotherapy, targeted therapy, clinical trials

Takeaways

Keynote 716 focuses on adjuvant treatment for stage 2 melanoma.

The trial shows benefit for pembrolizumab in stage 2B and 2C.

There are challenges in treating early-stage melanoma effectively.

The hazard ratio for pembrolizumab is around 0.6 for stage 2.

Accurate biomarkers are needed for early-stage melanoma.

The majority of melanoma patients are diagnosed at stage 1 or 2.

Local and regional recurrences are concerning for patients.

The conversation around treatment options continues to evolve.

Titles

Keynote 716: A New Era for Stage 2 Melanoma

The Challenges of Treating Early-Stage Melanoma

Sound Bites

"This is basically adjuvant treatment for stage 2 melanoma."

"Keynote 716 was a randomized phase three trial."

"DMFS is really our most relevant endpoint for adjuvant trials."

Chapters

00:00 Introduction

02:38 Quickfire Questions and Introduction to Keynote 716

04:31 Keynote 716 Trial Design and Results

06:41 Interpreting DMFS and Regional Recurrence

08:40 Overlap Between Stage Two and Stage Three

10:58 Exploring Combination Therapy for Recurrence

13:15 Testing for BRAF Mutations in Stage Two

17:00 Reimbursement and Timing of Mutational Testing

22:18 Reimbursement Issues and Quick Results for Mutational Testing

25:00 Summary and Closing Remarks

Summary

James is injured! Hear about his favorite style of exercise (strength v cardio), and his no excuses attitude towards aches, pains, and niggles.

In this episode, Sapna and James discuss the Keynote 054 study, which examines the efficacy of adjuvant pembrolizumab (Pembro) versus placebo in patients with resected stage 3A to 3C melanoma. They explore the study's design, results, and implications for treatment decisions, particularly regarding toxicity management and the challenges of interpreting crossover designs. The discussion also touches on the significance of endocrine side effects and the importance of using minimal immunosuppression to maintain treatment efficacy.

Keywords

melanoma, adjuvant therapy, Keynote 054, toxicity management, immune activation, treatment decisions, PD-1 therapy, melanoma research, cancer treatment, clinical trials

Takeaways

Adjuvant Pembro shows significant RFS benefit compared to placebo.

Crossover design complicates treatment decisions in clinical practice.

Toxicity management is crucial for patient safety and treatment efficacy.

Endocrine side effects may indicate immune activation and treatment sensitivity.

Minimal immunosuppression is recommended to avoid blunting treatment effects.

The hazard ratio for benefit is similar across melanoma stages.

Real-world treatment decisions often deviate from trial protocols.

Understanding toxicity trends is essential for effective management.

Patients with endocrine side effects may not require high-dose steroids.

Keynote 054 highlights the need for careful interpretation of adjuvant therapy results.

Sound Bites

"Adjuvant Pembro for a year versus placebo."

"Significant RFS benefit in comparison with placebo."

"The now or later question is inevitable."

Chapters

00:00 Introduction and Quick Fire Questions

03:25 Keynote 054: Adjuvant Pembrolizumab in Stage 3 Melanoma

10:48 Managing Toxicity in the Adjuvant Setting

Summary

In this conversation, Sapna Patel and James Larkin discuss the Checkmate 238 landmark study on adjuvant therapy for melanoma. They touch on various topics, including food choices, pets, and the study design. They highlight the importance of considering the heterogeneity and tempo of melanoma in treatment decisions. They also discuss the challenges of conducting dedicated trials for mucosal and acral melanoma subtypes. Overall, the Checkmate 238 study established the use of adjuvant anti-PD-1 therapy and has long-term follow-up data.

Keywords

melanoma, adjuvant therapy, Checkmate 238, study design, heterogeneity, tempo, mucosal melanoma, acral melanoma

Takeaways

Sound Bites

"Unconditionally loyal. Yeah, if only men were like this, right? Yeah, just kidding."

"If you compare the EORTC study with the Checkmate238 study, does NIVO have an OS benefit?"

"Patient selection for treatment is really, really important."

Chapters

00:00 Introduction and Quick Fires

03:12 The Checkmate 238 Landmark Study

08:17 Patient Selection and Challenges in Mucosal and Acral Melanoma

13:05 The Importance of Tempo and Risk of Relapse

16:17 The Need for Dedicated Trials in Mucosal and Acral Melanoma

In this conversation, James Larkin and Sapna Patel discuss the SWOG adjuvant study in melanoma. They cover topics such as the study design, the use of adjuvant anti-PD-1 therapy, the comparison with interferon and ipilimumab, and the potential side effects of adjuvant treatment. They also touch on the importance of risk-benefit discussions with patients and the need for biomarkers to predict toxicity. Overall, the study showed a benefit in recurrence-free survival with adjuvant pembrolizumab, but there was no significant overall survival benefit.

Keywords

SWOG adjuvant study, melanoma, adjuvant therapy, anti-PD-1, interferon, ipilimumab, side effects, risk-benefit discussion, biomarkers

Takeaways

The SWOG adjuvant study in melanoma showed a benefit in recurrence-free survival with adjuvant pembrolizumab.

There was no significant overall survival benefit in the study.

Adjuvant anti-PD-1 therapy is less toxic than adjuvant interferon or ipilimumab.

Risk-benefit discussions with patients are important in the adjuvant setting.

Biomarkers to predict toxicity would be helpful in guiding treatment decisions.

Titles

The need for biomarkers to predict toxicity

Understanding the side effects of adjuvant treatment

Titles

The need for biomarkers to predict toxicity

Understanding the side effects of adjuvant treatment

Sound Bites

"The SWOG S1404 study remains the largest adjuvant anti-PD-1 study completed in melanoma."

"This study sort of gets buried, but maybe for other reasons, I can tell you there are probably important reasons to pay attention to it."

"The risk of long-term irreversible side effects is a consideration in the adjuvant setting."

Chapters

00:00 Introduction and Quickfire Questions

02:03 The SWOG adjuvant study: Recurrence-free survival benefit

04:52 The underappreciated importance of the study

11:26 Understanding the side effects of adjuvant treatment

15:39 The analogy of adjuvant therapy to a self-driving car

19:47 Patient perception of benefit and risk

20:16 Conclusion

In this conversation, Sapna Patel and James Larkin discuss the EORTC 18071 study, which compared adjuvant ipilimumab to placebo in patients with stage III melanoma. They explore the use of adjuvant interferon in the past and the controversies surrounding its overall survival benefit. They also discuss the tolerability and side effects of ipilimumab, as well as the potential reasons for the survival benefit seen in the EORTC 18071 study. The conversation concludes with a summary of the study's findings.

Keywords

adjuvant therapy, ipilimumab, placebo, stage three melanoma, EORTC 18071 study, adjuvant interferon, overall survival benefit, tolerability, side effects, survival benefit

Takeaways

The EORTC 18071 study showed a significant overall survival benefit with adjuvant ipilimumab in patients with stage three melanoma.

The use of adjuvant interferon in the past was controversial, with a loss of overall survival benefit over time.

Ipilimumab has significant side effects and can impact patients' quality of life.

The survival benefit seen in the EORTC 18071 study may be due to the early use of CTLA-4 blockade in the immune sequence.

The subsequent use of PD-1 therapy as salvage treatment may explain the lack of overall survival benefit in other checkpoint inhibitor adjuvant trials.

Titles

Potential Reasons for Survival Benefit in the EORTC 18071 Study

Tolerability and Side Effects of Ipilimumab in Adjuvant Therapy

Sound Bites

"This was our only study that actually has overall survival benefit in the adjuvant setting using checkpoint inhibitor."

"The use of adjuvant interferon really dwindled when that OS benefit was lost."

"We would tell patients, you will know you're on treatment and you will walk around feeling like you have the flu."

Chapters

00:00 Introduction and Quick Fire Questions

02:05 Overview of the EORTC 18071 Study

06:11 Tolerability and Side Effects of Ipilimumab

11:06 Potential Reasons for Survival Benefit in EORTC 18071 Study

14:25 Wrap-up of Ipilimumab Discussion

Summary

In this conversation, James Larkin and Sapna Patel discuss the findings of the Checkmate 204 study, which looked at the treatment of brain metastases from melanoma using nivolumab and ipilimumab. They highlight that the combination therapy showed efficacy in asymptomatic patients with brain metastases, with a 55% intracranial clinical benefit rate. They also discuss the importance of early detection and treatment of brain metastases, as well as the role of local therapies such as surgery and stereotactic radiotherapy. The conversation emphasizes the need to minimize the use of steroids and start systemic treatment as soon as possible.

Keywords

Checkmate 204, brain metastases, melanoma, nivolumab, ipilimumab, intracranial clinical benefit, asymptomatic, local therapy, surgery, stereotactic radiotherapy, steroids, systemic treatment

Takeaways

Sound Bites

"NIVO-IPI is active in the brain for asymptomatic patients."

"If you have an asymptomatic untreated brain met measuring at least 0.5 centimeters, there's activity with this combination."

"When I was learning how to treat this disease 20 years ago, having brain metastasis was basically a death sentence. Now we're talking about three-year data and it looks like the possibility of cure in some of these patients."

Chapters

00:00 Introduction and Overview of Checkmate 204

06:33 Improvement in Outcomes for Brain Metastases

11:47 Importance of Early Detection and Treatment

23:16 Practical Considerations and Conclusion

25:38 Fact Check