Summary

James' favorite moments from #ESMO24 include footie and a not-so-chance encounter with NEJM Editor-in-Chief, Eric Rubin.

In this episode of Melanoma Matters, hosts Sapna Patel and James Larkin discuss the Relativity 020 study, which focuses on Nivo Rela after PD-1 exposure in melanoma patients. They reflect on their experiences at ESMO, including networking and memorable moments, before diving into the details of the study, including patient cohorts, treatment efficacy, and the challenges faced in clinical trials. The conversation also touches on the role of CTLA-4 therapies and the complexities of treatment sequencing in melanoma care.

Keywords

melanoma, ESMO, Relativity 020, Nivo Rela, PD-1, CTLA-4, clinical trials, patient access, immunotherapy, oncology

Takeaways

The Relativity 020 study explores Nivo Rela after PD-1 exposure in melanoma.

Networking at ESMO is crucial for sharing insights and experiences.

Patient access to treatments is a significant challenge in clinical trials.

The efficacy of Nivo Rela in heavily pretreated patients is limited.

CTLA-4 therapies show low response rates in PD-1 refractory patients.

Understanding treatment sequences is essential for optimizing patient outcomes.

The importance of academic trials in addressing knowledge gaps in melanoma treatment.

Elevated LDH levels are a concerning biomarker in treatment response.

Collaboration among investigators is vital for advancing melanoma research.

The conversation highlights the need for ongoing research and trials in melanoma.

Chapters

00:00 Introduction and ESMO Highlights

03:30 Reflections on ESMO 2024

06:21 The Relativity 020 Study Overview

09:17 Patient Perspectives and Clinical Trials

12:20 Challenges in European Clinical Trials

15:36 Efficacy of NIVO-RELA in Refractory Melanoma

18:40 Discussion on CTLA-4 Therapies

21:21 Future Directions in Melanoma Treatment

Summary

In this episode of Melanoma Matters, hosts James Larkin and Sapna Patel reflect on their experiences at ESMO 2024 and the importance of face-to-face meetings. But then James pops the balloon by commenting on the carbon footprint of the airplane travel. They go on to discuss the phase three trial comparing ipilimumab doses in melanoma and delve into the trial's design, results, and implications for clinical practice. The conversation also covers the significance of long-term follow-up data, the challenges of pooled analyses, and the need for improved clinical trial design to capture more nuanced survival data.

Keywords

melanoma, ipilimumab, clinical trials, ESMO, cancer treatment, immunotherapy, overall survival, phase three trial, patient care, research

Takeaways

The value of face-to-face meetings is irreplaceable.

The IP10 trial was crucial for understanding ipilimumab dosing.

Access to effective treatments can be limited by bureaucracy.

Long-term follow-up data is essential for understanding treatment efficacy.

Re-challenging with ipilimumab can be effective in certain cases.

Pooled analyses can provide insights but have limitations.

Clinical trial design should capture more than just overall survival.

Data quality varies between industry and academic studies.

Understanding the mechanisms of resistance is key to treatment.

Dosing strategies in immunotherapy require careful consideration.

Sound Bites

"My favorite is just being within vibrational energy of people you hold dear."

"We had a queue of patients waiting to go into the study."

"This study was really trying to answer in a prospective way."

Chapters

00:00 Introduction and Icebreaker Moments

03:41 Discussion on the Phase Three IP10 Trial

06:15 Trial Design and Results Overview

09:04 Clinical Implications and Treatment Access

12:01 Re-challenging with Ipilimumab

14:55 Long-term Follow-up and Survival Rates

18:07 The Importance of Data Quality in Trials

20:19 Conclusions and Final Thoughts

Summary

In this episode, James needs some sun cream! The conversation discusses the outcomes of post-recurrence systemic therapy following adjuvant checkpoint inhibitor treatment for resected melanoma in the Checkmate 238 trial. The study found that early recurrences were associated with worse outcomes compared to late recurrences. Patients who recurred early had shorter progression-free survival and overall survival compared to those who recurred later. The subsequent therapy received by patients varied, with some receiving chemotherapy, immunotherapy, or targeted therapy. The data on subsequent therapy were not well-categorized, making it difficult to draw definitive conclusions. The conversation highlights the challenges of treating patients who recur despite adjuvant therapy and the need for further research in this area.

Keywords

melanoma, adjuvant therapy, recurrence, systemic therapy, checkpoint inhibitors, progression-free survival, overall survival, subsequent therapy

Takeaways

• Early recurrences in melanoma patients who received adjuvant checkpoint inhibitor therapy are associated with worse outcomes compared to late recurrences.
• The subsequent therapy received by patients varied, with some receiving chemotherapy, immunotherapy, or targeted therapy.
• The data on subsequent therapy were not well-categorized, making it difficult to draw definitive conclusions.
• Treating patients who recur despite adjuvant therapy remains a significant challenge in clinical practice.

Sound Bites

"Early recurrences in melanoma patients are a bad thing."

"Sensitivity to anti-PD-1 drugs is not black and white; there are gray zones."

"The subsequent therapy received by patients varied, with some receiving chemotherapy, immunotherapy, or targeted therapy."

Chapters

00:00 Introduction and Personal Experiences with Sunburns

05:00 Overview of Checkmate 238 and Outcomes after Recurrence

09:58 Early versus Late Recurrences and Treatment Outcomes

16:58 Analysis of Recurrence Patterns and Subsequent Therapies

23:58 Discussion on Anatomic Sites of Recurrence

29:27 Conclusion and the Importance of Further Research

30:30 Fact Check

31:54 The Search for Clinically Usable Biomarkers

32:20 Acknowledging Efforts

Summary

(Coach) Owen is in a seriously bad mood with James at the moment! But James is back in pull-up form and can do an impressive number of strict pull-ups...

In this episode, Sapna Patel and James Larkin discuss the LEAP 004 and LEAP 003 studies, focusing on the combination of lenvatinib and pembrolizumab in treating melanoma, particularly in patients who are refractory to PD-1 inhibitors. They explore the efficacy, safety, and implications of these studies, as well as the challenges in treatment guidelines and future directions for research in this area.

Keywords

melanoma, LEAP 004, lenvatinib, pembrolizumab, clinical trials, cancer treatment, efficacy, safety, guidelines

Takeaways

The LEAP 004 study showed a 21.4% response rate.

Lenvatinib is a multi-targeted VEGF receptor inhibitor with potential in melanoma.

The combination of lenvatinib and pembrolizumab may increase sensitivity to PD-1 inhibitors.

Toxicity is a significant concern with the lenvatinib and pembrolizumab combination.

LEAP 003 did not demonstrate an improvement in overall survival compared to pembrolizumab alone.

The efficacy of lenvatinib in melanoma is still being evaluated in refractory settings.

There is a need for further studies to understand the mechanisms of resistance to PD-1 therapy.

Guidelines for treatment may vary significantly between jurisdictions.

Patient perspectives on treatment and toxicity are crucial in clinical practice.

The future of lenvatinib and pembrolizumab in melanoma treatment remains uncertain.

Sound Bites

"What's your number of kilos you're deadlifting?"

"Lenvatinib has been around for a while."

"The unmet need we all know, which is anti PD-1 refractory melanoma."

Chapters

00:00 Introduction and Discussion of Deadlifting

03:31 Overview of Leap004 Study and Rationale for Lenvatinib

09:22 Promising Results in Leap004 Study

15:59 Discontinuation of Leap003 Trial

19:33 Challenges with Dosing and Toxicity of Lenvatinib

22:00 Uncertainty in the Use of Lenvatinib-Pembrolizumab in PD-1 Refractory Patients

Summary

On the heels of the great ESMO 2024 session with Toni Ribas, Inge Marie Svane, and Olivier Michielin James and Sapna discuss Prof Svane and Prof van Haanen's TIL trial, a significant study in melanoma treatment that explores the efficacy and safety of tumor-infiltrating lymphocyte (TIL) therapy compared to traditional treatments. They delve into the historical context of the trial, its design, the observed efficacy rates, potential side effects, and the implications of sex-based differences in treatment outcomes. The discussion highlights the importance of this trial in shaping future treatment strategies for melanoma and the need for further research in this area.

Keywords

TIL trial, melanoma, cellular therapy, immunotherapy, efficacy, toxicity, first-line treatment, sex-based differences

Takeaways

The TIL trial is a landmark study in melanoma treatment.

TIL therapy shows a near 50% response rate in patients.

The control arm of the trial has faced criticism.

TIL therapy is a viable strategy for patients after PD-1 exposure.

Toxicity profiles of TIL therapy need careful consideration.

There is potential for TIL therapy to be used in first-line treatment.

Sex-based differences in treatment outcomes are significant.

The trial design raises important regulatory questions.

Further research is needed to understand hormonal influences on treatment.

The results of this trial could change treatment paradigms in melanoma.

Sound Bites

"This is the first randomized study of cellular therapy."

"TIL therapy shows a near 50% response rate."

"The control arm has been criticized."

Chapters

00:00 Introduction to the TIL trial

04:08 Discussion on the efficacy of TIL therapy

09:12 Considerations for regulatory approval and future research

11:34 Analysis of toxicity in the TILT trial

15:46 Exploring the potential of TIL therapy in the first-line setting

20:12 Discussion on the feasibility of conducting larger trials with TIL therapy

23:42 Sex-based differences in the response to TIL therapy

27:35 Complexity of studying sex-based differences in cancer treatment

31:04 Conclusion and future implications of the TILT trial

33:07 Impressive Median Dose of Till Cells

33:33 Administration of High-Dose IL-2

Summary

In this episode of Melanoma Matters, host James Larkin uses his 1-800-Operator voice until co-host Sapna Patel reminds him to use his podium voice. There is a noisy wardrobe choice (SP) and a fact check of a fact check (JL).

Sapna and James have an in-depth conversation of the Checkmate 511 study, discussing its implications for treatment regimens in melanoma. They delve into the nuances of type 1 and type 2 errors, analyze the results of the study, and consider the long-term follow-up data. The conversation also explores global perspectives on treatment practices and the importance of understanding toxicity and efficacy in clinical settings.

Keywords

Checkmate 511, melanoma, type 1 error, type 2 error, treatment regimens, efficacy, toxicity, global perspectives, long-term follow-up, clinical practice

Takeaways

Checkmate 511 is a widely cited study in melanoma treatment.

Type one error relates to the alpha of the study, while type two error is related to sample size.

The study showed a lower incidence of grade 3 to 5 AEs with Nivo 3 - Ipi 1 compared to Nivo 1 -Ipi 3.

Long-term follow-up is crucial for understanding the efficacy of treatment regimens.

Global perspectives on treatment regimens vary, especially regarding reimbursement and labeling.

The study's findings have influenced practice in the U.S., despite a lack of formal publication.

Concerns remain about the efficacy of lower doses in specific patient populations, such as those with brain metastases.

The conversation highlights the importance of ongoing research and follow-up studies in melanoma treatment.

Understanding statistical errors is essential for interpreting clinical trial results.

The hosts express a desire for more comprehensive data and follow-up on the Checkmate 511 study.

Sound Bites

"This is a fact check of a fact check."

"Type one error is related to the alpha of a study."

"The incidence of grade 3 to 5 AEs was 34% with Nivo 3 -Ipi 1."

Chapters

00:00 Introduction and Volume Issues

04:50 Overview of Checkmate 511 Study

09:59 Concerns about Lack of Published Follow-Up Data

16:00 Demographics and Subgroups in Checkmate 511 Study

16:44 Implementation of Inverted Dosing Regimen Globally

19:01 Caution and Considerations with Inverted Dosing Regimen

23:45 Fact Check

25:08 Comparing Regimens in the BRAF Mutant Population

29:16 Fact-Checking 'Up in the Air'

29:50 Fact Check of a Fact Check (BRAF)

Summary

James is back from holiday and tells us the peak, pit, and bud of his time away. (Spoiler: the pit was NOT a broken tooth!) He also shares a tip for time management and email hygiene on holiday. Sapna makes an unfortunate wardrobe choice (noisy, not visual).

In this episode of Melanoma Matters, hosts Sapna and James delve into the complexities of indirect treatment comparisons in melanoma therapy. They discuss a recently published paper comparing nivolumab plus relatlimab versus nivolumab plus ipilimumab, exploring the statistical methodologies, clinical implications, and biological plausibility of the findings. The conversation highlights the importance of understanding treatment options, patient selection, and future directions in melanoma treatment strategies.

Keywords

melanoma, indirect treatment comparison, nivolumab, relatlimab, ipilimumab, clinical trials, biomarkers, treatment strategies, patient care, oncology

Takeaways

Indirect treatment comparisons are a valid methodology.

Statistical methodologies can be complex but are essential for comparisons.

The efficacy of treatments can vary based on patient characteristics.

Biological plausibility is crucial in interpreting treatment outcomes.

LDH levels can be significant biomarkers in treatment decisions.

Ipilimumab plus nivolumab is considered a potent treatment regimen.

Patient experience and clinical data inform treatment choices.

Future strategies may involve combining therapies for better outcomes.

Understanding the nuances of clinical trials is vital for practitioners.

Reimbursement discussions may hinge on the findings of such studies.

Sound Bites

"I don't understand the statistics and the principles behind it."

"It's an accepted methodology, I think is the first thing to say."

"It's a reasonable exercise."

Chapters

00:00 Introduction and Rapid Fire Questions

06:49 Understanding Indirect Treatment Comparison

11:55 Comparison of Nevolumab Plus Relatlimab vs. Nevolumab Plus Ipilimumab

14:40 LDH as a Biomarker in Melanoma

20:28 Benefit of Ipnevo for BRAF Mutated Patients

23:17 Considerations for Targeted Therapy Before Immunotherapy

Summary

Our hosts guilty pleasures - junk food and South Park! Endless laughs about South Park...

In this episode of Melanoma Matters, Sapna Patel and James Larkin discuss the complexities of end-of-life care in patients with melanoma. They explore the importance of early conversations about treatment options, the role of palliative care, and the emotional and cultural aspects of dying. The discussion emphasizes the need for clear communication with patients regarding their treatment goals and the transition to palliative care as the disease progresses.

Keywords

melanoma, end of life, palliative care, treatment decisions, steroid use, goals of care, symptom management, cultural perspectives

Takeaways

• End-of-life conversations should start early in treatment.
• Palliative care teams can provide essential support.
• Patients often feel better initially on targeted therapies.
• Cultural perspectives influence how patients view death.
• It's crucial to listen to patients' feelings about their treatment.
• Transitioning to palliative care requires careful planning.
• Symptom management is a key focus in end-of-life care.
• Communication with families is vital for understanding wishes.
• Patients may resist discussions about end-of-life care.
• Healthcare providers must be comfortable discussing death.

Titles

The Importance of Early Goals of Care

Navigating End of Life in Melanoma Care

Sound Bites

"What's the minimal amount of therapy?"

"Transitioning to a different phase of treatment."

"It's important to have those conversations early."

Chapters

00:00 Introduction and Guilty Pleasures

05:21 Transitioning to Non-Curative Treatment

09:39 Early Goals of Care Discussions

11:55 The Limitations of BRAF Targeted Therapy

14:07 Connecting Patients to Palliative Care

15:59 Options for End-of-Life Care

16:29 Challenges of Delivering Nursing Care at Home

17:32 Limitations of Hospice Care

19:50 The Role of Targeted Therapies in Palliative Care

24:06 Managing Symptoms with Steroids

33:20 Medical Assistance in Dying

Summary

In this episode of Melanoma Matters, hosts James Larkin and Sapna Patel discuss a couple of liver-directed trials in metastatic uveal melanoma. They focus on the CHOPIN and SCANDIUM trials, the combination of liver-directed therapies with systemic treatments, and the safety and efficacy of these approaches. The conversation highlights the innovative efforts of European investigators and the need for adaptive trial designs in rare diseases.

Keywords

melanoma, uveal melanoma, SCANDIUM, CHOPIN, liver directed therapy, systemic therapy, checkpoint inhibitors, cancer research, clinical trials, treatment options

Takeaways

We have limited treatment options for metastatic uveal melanoma.

Combining liver-directed therapy with systemic therapy is being explored.

Future trials are needed to understand optimal sequencing of therapies.

Adaptive trial designs may be challenging in rare cancers.

European investigators are leading innovative trials in this field.

The importance of collaboration in cancer research is emphasized.

Sound Bites

"We have a couple of approved agents."

"Is it safe to combine these therapies?"

"The IHP treatment had a superior response rate."

Chapters

00:00 Introduction and Icebreaker Question

01:52 Background and Objectives of the Studies

04:17 Results and Conclusions of the Scandium, Scandium-2, and Chopin Studies

06:28 Feasibility of Adaptive Trials for Rare Cancers

08:52 The Importance of International Collaboration in Uveal Melanoma Research

09:48 Closing Remarks and Future Directions

Summary

Warning: we recorded ANOTHER 40-minute episode on uveal melanoma! But this time we decided *not* to split it into 2 episodes. So dig in for a long one...there's the use of props at the end!

In this conversation, James and Sapna discuss the FOCUS trial and the use of the melphalan hepatic delivery system. The discussion highlights the importance of understanding the differences between infusion and perfusion, the implications of study design on dropout rates, and the future directions for treatment in this area.

Takeaways

The FOCUS trial showed a high dropout rate due to unappealing control arms.

Melphalan hepatic delivery is a new approach for treating uveal melanoma.

Understanding the difference between infusion and perfusion is crucial for treatment efficacy.

Patient selection is key, especially regarding liver involvement.

The objective response rate of 36.3% is significant for this patient population.

Quality of life post-treatment has improved compared to previous methods.

The study design faced challenges due to high dropout rates.

Future studies may need to consider alternative endpoints for efficacy.

The treatment requires a specialized care team for administration.

Overall survival data is still pending for the new treatment approach.

Keywords

melphalan, HDS, uveal melanoma, FOCUS trial, treatment efficacy, patient selection, infusion, perfusion, clinical trials, oncology

Sound Bites

"This is a pitiful fact check."

"The hazard ratio for that study for OS was basically one."

"It's not a closed system of catheters."

Chapters

00:00 Introduction and Icebreaker

02:31 Overview of the FOCUS Trial

05:09 Designing Clinical Trials with Challenging Control Arms

08:50 Procedure and Treatment Details

18:30 Objective Response Rate and Duration of Response

20:49 Side Effects and Considerations for Patient Selection

33:24 Fact Check

34:07 Dropout in the FOCUS Trial and the Checkmate 037 Study

36:47 Infusion versus Perfusion - what's the difference

39:54 Clarifying the M Category for Melanoma