Summary

Find out which host is a french fry aficianado, who loves a doner kebab as a guilty pleasure, and other cheeky indulgences (Lebowski's, Gettysburger, Union Rings, Freedom Fries, Law & Order: SVU...)

In this conversation, hosts Sapna Patel and James Larkin discuss the latest findings and studies related to uveal melanoma treatments, particularly focusing on the combination of nivolumab and ipilimumab. They explore the differences in treatment outcomes between studies conducted in Spain and the US, the efficacy of these treatments, and the implications for future research and clinical practice.

Keywords

Uveal melanoma, nivolumab, ipilimumab, treatment studies, immune checkpoint inhibitors, clinical trials, response rates, survival curves, adverse events, cancer research

Takeaways

Nivolumab and ipilimumab are key treatments for uveal melanoma.

The Spanish study showed an objective response rate of 11.5%.

The US study had a higher response rate of 19%.

Adverse events differ between studies, indicating potential global differences.

Genotyping of patients is crucial for understanding treatment responses.

The primary endpoints of the studies were different, affecting comparisons.

Combination therapies may offer additive or synergistic effects.

Monitoring liver enzymes is essential during treatment.

Response characteristics can inform future treatment decisions.

Sequencing treatments may enhance patient outcomes in uveal melanoma.

Titles

Exploring Uveal Melanoma Treatments

Nivolumab and Ipilimumab: A Deep Dive

Chapters

00:00 Introduction and Guilty Pleasures

03:40 Efficacy of Ipilimumab and Nivolumab in Uveal Melanoma

10:59 Sequencing Strategies and Biomarkers in Uveal Melanoma

14:47 Long-Term Survival in Uveal Melanoma

16:41 Monitoring Liver Enzymes in Checkpoint Inhibitor Therapy

24:09 Fact Check: Nivolumab Plus Ipilimumab in Uveal Melanoma Studies

26:38 Efficacy Metrics: GEM 1402 Study vs. MD Anderson Study

27:35 Adverse Events: Spanish Study vs. US Study

28:32 Publication and Editorial in Journal of Clinical Oncology

Summary

Hosts James Larkin and Sapna Patel have a bit of fun around the words juice, wimpy, lobster red, and 3 inches. The conversation about tebentafusp in uveal melanoma continues, focusing on the concept of treating beyond progression, the tolerability of treatments, survival outcomes, and the implications of HLA frequency in patient selection for clinical trials. The speakers discuss the importance of patient communication regarding treatment options, the management of side effects, and the evolving landscape of cancer therapies.

Keywords

treatment beyond progression, uveal melanoma, survival curves, IPI NIVO, HLA frequency, cytokine release syndrome, patient tolerability, cancer treatment, clinical trials, immunotherapy

Takeaways

Treating beyond progression can still yield benefits for patients.

Most side effects from treatment are low grade and manageable.

Patients often tolerate maintenance treatment well with minimal adverse effects.

Survival curves for uveal melanoma show significant improvements over time.

Comparative studies suggest TEBE may outperform IPI NIVO in survival rates.

HLA frequency is crucial understanding screening numbers in clinical trials.

Understanding cytokine release syndrome is essential for managing patient care.

Patient education on treatment options is vital for informed decision-making.

The landscape of uveal melanoma treatment is evolving.

Future research is needed to clarify HLA type frequencies across populations.

Sound Bites

"treatment beyond progression and had an analysis"

"the good news is they're almost always low grade"

"they can tolerate it and you don't have a lot of problems"

Chapters

00:00 Exploring Tebentafusp for Uveal Melanoma

01:31 Liver involvement in metastatic uveal melanoma

03:22 Tolerability of Tebentafusp and common side effects

10:50 Exploring long-term disease control and comparisons to other treatments

17:00 Investigating the frequency of HLA type in the population

19:32 Fact Checking and Supplemental Data

20:50 KIMMTRAK Connect for Patient Treatment

21:54 HLA Frequency in the Brazilian Population

22:22 Propensity Score Study: Tebentafusp vs. Frontline Ipi-Nivo

Summary

Step aerobics, DOMS, and Princess Diana all in one opening story. In this episode of Melanoma Matters, hosts James Larkin and Sapna Patel discuss the drug tebentafusp and its implications in treating uveal melanoma. They explore the study design, patient demographics, and the significance of overall survival rates in clinical trials. The discussion highlights the innovative nature of tebentafusp as a first-in-class drug and its potential benefits over traditional treatments.

Keywords

Tebentafusp, Uveal Melanoma, Immunotherapy, Cancer Treatment, Clinical Trials, Overall Survival, Checkpoint Inhibitors, T Cell Receptor, Phase 3 Trials, Patient Demographics, HLA

Takeaways

Tebentafusp is a first-in-class drug for uveal melanoma.

The study showed an improvement in overall survival from 16 months to 21.7 months.

High resolution genotyping is essential for patient selection.

Dacarbazine has been shown to have a 0% response rate in trials for uveal melanoma.

The study was a global effort with significant patient enrollment.

Patients with liver involvement are predominant in metastatic uveal melanoma.

The hazard ratio of 0.51 indicates a strong treatment effect.

Demographics play a crucial role in understanding treatment outcomes.

Understanding the mechanism of action is vital for future research.

Titles

The Role of Genotyping in Cancer Treatment

The Impact of Tebentafusp on Patient Survival

Sound Bites

"This is a first in class drug."

"Tebentafusp improves overall survival."

"The hazard ratio is very striking."

Chapters

00:00 If I weren't a doctor...

07:18 Tebentafusp in uveal melanoma

14:04 Inclusion Criteria for IMC gp100-202 Study

16:42 Different AJCC Criteria for Uveal Melanoma and Cutaneous Melanoma

18:34 Liver involvement in metastatic uveal melanoma

21:30 Exploring long-term disease control and comparisons to other treatments

22:00 Splitting the Episode into 2 Parts

Summary

James recalls a concert in Juan-les-Pins in Antibes, France where he saw one of the best performances he can remember (swanky locale under the pines). And a tip of the hat to the Wedding Present whose gigs he says were "always amazing"

In this episode of Melanoma Matters, James and Sapna discuss the long-term follow-up results of the COMBI-AD study, which evaluates the efficacy of adjuvant therapy in melanoma patients with BRAF mutations. They delve into the statistical significance of the results, discuss the V600K subset, and explore the implications of subsequent therapies on overall survival. The conversation emphasizes the importance of patient-centric approaches in treatment decisions and the need for ongoing research in the field of melanoma.

Keywords

COMBI-AD, dabrafenib, trametinib, melanoma, adjuvant therapy, V600E, V600K, overall survival, RFS, targeted therapy, immunotherapy, long-term follow-up

Takeaways

Titles

COMBI-AD: A Decade of Data

Sound Bites

"This is the longest follow-up we've ever seen."

"The OS has a P value of 0.0000-something."

"V600K patients have an RFS benefit."

Chapters

00:00 Best Concert

04:32 Overview of the COMBI-AD Trial

07:09 Analysis of Overall Survival and Subgroups

10:54 Subsequent Therapies in the COMBI-AD Trial

17:09 Exploratory Analysis of Subgroups by Subsequent Therapy

19:56 Considerations for V600K Patients in the Adjuvant Setting

22:58 The Role of Adjuvant Therapy and Individualized Treatment Decisions

25:37 Long-term Follow-up Data and Counseling Patients

Summary

Hosts Sapna Patel and James Larkin discuss what they're currently watching on tv & streaming services. (Spoiler: Eric Cartman on Ozempic)

The main conversation delves into the Relativity 48 study of triple immune checkpoint inhibition presented at ASCO 2024. The hosts discuss the study's design, patient characteristics, safety profile, and efficacy results, highlighting the importance of understanding the implications of this new treatment regimen. They also explore future directions for research and the potential impact on clinical practice.

Keywords

Relativity 48, melanoma, triple therapy, immune checkpoint inhibitors, safety, efficacy, ASCO 2024

Takeaways

Titles

Relativity 48: What We Learned from ASCO 2024

Triple Therapy for Melanoma: Safety and Efficacy Insights

Sound Bites

"100% of patients had an adverse event."

"Median PFS has not been reached yet."

"The objective response rate was 59%."

Chapters

00:00 Introduction and TV Preferences

02:55 Overview of the Relativity 48 Study

09:20 Safety Profile of the Triple Therapy

15:39 Objective Response Rate and Independent Central Review

18:23 Progression-Free Survival and Follow-Up

24:00 Exploring Higher Doses of Ipilimumab and Future Trials

31:45 Fact Check

Summary

How many countries are there in the world? 195 according to the United Nations. (Host James Larkin nearly got it right)

In this episode of Melanoma Matters, Sapna and James discuss recent developments in melanoma treatment, focusing on the FDA's recent ODAC vote regarding neoadjuvant trial designs and the implications of the Nadina data. They explore the importance of pathology in treatment decisions, the challenges of regulatory approval and reimbursement, and the significance of biomarkers in determining treatment efficacy. The conversation also highlights the need for training pathologists to ensure accurate assessments and the future directions in melanoma treatment, particularly for patients who do not respond to current therapies.

Keywords

Melanoma, FDA, ODAC vote, Neoadjuvant therapy, Adjuvant therapy, Clinical trials, Biomarkers, Pathology, Regulatory approval, Reimbursement, Oncology

Takeaways

The FDA's recent vote emphasizes the need for clear trial designs.

Nadina data provides valuable insights into neoadjuvant therapy.

Pathology plays a crucial role in treatment decision-making.

Event-driven trials can lead to earlier conclusions on sample sizes.

Neoadjuvant therapies offer better outcomes than adjuvant therapies.

Biomarkers are essential for predicting treatment responses.

Training pathologists is vital for improving patient outcomes.

Future treatments should focus on patients who do not respond to current therapies.

Regulatory approval is necessary for treatment reimbursement.

Understanding the nuances of trial designs is critical for future research.

Sound Bites

"Nadina data shows promise for melanoma treatment."

"Pathology is critical for treatment decisions."

Chapters

00:00 Introduction and Icebreaker

03:13 Discussion on the Nadina Trial Results

09:05 Challenges of Regulatory Approval and Reimbursement

13:23 The Role of Biomarkers in Treatment Decisions

24:18 The Importance of Training and Standardization in Pathology Review

27:43 The Implications of the FDA ODAC Vote

28:27 Fact Check

28:30 **Re-take** FDA Vote on Neoadjuvant Trial Design

29:51 Isolating the Contribution of Components and Phases

31:27 Explicitly Addressing Questions in Trial Design

31:40 The Potential Need for Multiple Arms in Trials

33:15 Fact check of ODAC vote about AEGEAN trial

Summary

In this episode, Prof Christian Blank introduces us to a woman named NADINA. We find out what kind of car he drives as well as James when he's not cycling around London (hint: adoks backwards). We fixed the sound and video at the end, so you can have a laugh along with us.

Christian discusses with James and Sapna the NADINA trial, combination neoadjuvant therapy for melanoma. He emphasizes the importance of personalized treatment and the challenges faced in regulatory processes within oncology. The discussion highlights the significance of the trial's findings and the potential for improved patient outcomes through tailored therapies.

Keywords

Christian Blank, NADINA trial, immunotherapy, melanoma, oncology, neoadjuvant therapy, patient safety, personalized medicine, cancer research, regulatory issues

Takeaways

Christian Blank's journey reflects a deep passion for immunology.

The NADINA trial shows promising results for neoadjuvant therapy.

Neoadjuvant therapy can lead to quicker patient recovery.

Personalization of treatment is crucial for patient outcomes.

Safety remains a priority in cancer treatment.

Understanding patient responses can guide future therapies.

Regulatory challenges impact the implementation of new treatments.

The interferon signature is a key biomarker for treatment efficacy.

Collaboration between physicians and regulatory bodies is essential.

Continuous research is needed to improve cancer therapies.

Christian drives a Fiat, James drives a Skoda.

Sound Bites

"I fell in love with the immune system."

"The most important organ in our body."

"The neoadjuvant application of checkpoint inhibition is superior."

"60% of the patients are done after six weeks of therapy."

Chapters

00:00 Introduction and Career Background

05:03 The NADINA Trial: Neoadjuvant Therapy for Melanoma

10:52 Personalized Treatment Approaches and Biomarker Selection

21:51 Physician Responsibility and Changes in the Regulatory System

We dedicate this episode to our friend and colleague, Prof Jeff Weber (1952 - 2024).

In this conversation, Jeff discusses the best of ASCO 2024 for melanoma and skin cancers. He presents the findings of the V940 trial, which showed a benefit in recurrence-free survival and distant metastasis-free survival for a personalized mRNA neoantigen vaccine combined with pembrolizumab. He also discusses the potential of flip-dose ipi nivo toci and the future of adjuvant therapy. The conversation also covers the results of the NADINA trial, which showed promising event-free survival data for neoadjuvant PD-1 therapy. Jeff Weber shares his thoughts on the use of personalized vaccines in neoadjuvant and metastatic settings.

Keywords

ASCO 2024, melanoma, skin cancers, V940 trial, personalized mRNA neoantigen vaccine, Pembrolizumab, flip-dose ipi nivo toci, adjuvant therapy, NADINA trial, neoadjuvant PD-1 therapy, personalized vaccines, metastatic settings

Takeaways

The V940 trial demonstrated a benefit in recurrence-free survival and distant metastasis-free survival for a personalized mRNA neoantigen vaccine combined with Pembrolizumab.

Flip-dose ipi nivo toci shows promise in reducing toxicity associated with immune agents.

The NADINA trial showed promising event-free survival data for neoadjuvant PD-1 therapy.

The use of personalized vaccines in neoadjuvant and metastatic settings holds potential for improving outcomes in melanoma and skin cancers.

Takeaways

The V940 trial demonstrated a benefit in recurrence-free survival and distant metastasis-free survival for a personalized mRNA neoantigen vaccine combined with pembrolizumab.

Flip-dose ipi nivo toci shows promise in reducing toxicity associated with immune agents.

The NADINA trial showed promising event-free survival data for neoadjuvant PD-1 therapy.

The use of personalized vaccines in neoadjuvant and metastatic settings holds potential for improving outcomes in melanoma and skin cancers.

Sound Bites

"V940 or KEYNOTE 942 was a randomized phase 2 trial... showing a benefit in terms of recurrence-free survival."

"Any strategy that'll decrease toxicity will be welcomed."

"NADINA had definitely one of the worst kept secrets in oncology... it's going to be a positive study."

Chapters

00:00 Introduction and Background

03:20 Summary of the V940 Trial

08:18 Flip-Dose Ipi Nivo Toci and Reducing Toxicity

12:01 Promising Results from the NADINA Trial

14:29 The Future of Personalized Vaccines

16:21 Neoadjuvant and Metastatic Settings

Summary

James is ill (apparent in his voice)! Find out what gets James to show up to an ASCO meeting, and stay tuned for the fact check to hear the infamous tweet from Omid Hamid regarding James' scrubs.

In this episode of Melanoma Matters, hosts James Larkin and Sapna Patel discuss sequencing of immunotherapy and targeted therapy for BRAF-positive melanoma. They review the SECOMBIT study 4-year update from Nature Communications. The sandwich approach is unpacked as an approach to debulk the tumor and increase immune fitness of the patient. They also review lactate dehydrogenase as a selection criteria for treatment, the role of LDH, the phrase 'par excellence', the difference in impact factor between Nature journals, CNS incidence and autopsy series.

Keywords

SECOMBIT trial, BRAF positive melanoma, lactate dehydrogenase, LDH, immunotherapy, targeted therapy, CNS incidence, autopsy series

Titles

The Role of LDH

CNS Incidence and Autopsy Series

Sound Bites

"You're rocking the scrubs"

"How to define par excellence"

"Difference in impact factor"

Summary

In this conversation, Sapna puts Santa Fe, NM on the map of her all time favorite places in the USA.

James and Sapna go on to discuss the DreamSeq study, which focuses on the sequencing of systemic therapy in patients with BRAF mutant metastatic melanoma. They explore the historical context of melanoma treatments, the design and endpoints of the trial, and the implications for clinical practice. The discussion highlights the importance of treatment sequencing, the potential underestimation of benefits in the study, and considerations for future research and patient care.

Keywords

DreamSeq, melanoma, BRAF mutant, immunotherapy, targeted therapy, clinical trials, treatment sequencing, overall survival, patient outcomes, cancer research

Takeaways

Santa Fe, New Mexico is a personal favorite for quiet and art.

DreamSeq is a significant study in melanoma treatment.

The historical context of melanoma treatments is crucial for understanding current practices.

Immunotherapy may take time to show effects, impacting treatment sequencing.

The trial design of DreamSeq focused on overall survival as a primary endpoint.

Real-world applications of trial findings are essential for patient care.

The sequencing of therapies can significantly affect patient outcomes.

Understanding the tumor microenvironment is key in treatment decisions.

The choice of BRAF-MEK therapy may be less critical than the choice of immunotherapy.

Future studies should consider the incidence of brain metastases in treatment outcomes.

Titles

The Art of Sequencing: DreamSeq Explained

DreamSeq: A New Era in Melanoma Treatment

Sound Bites

"DreamSeq may even underestimate the benefit."

"Combination Nivo/ipi first should be the preferred treatment sequence."

"There's an optimal window for treatment sequencing."

Chapters

00:00 Optimizing Treatment Strategies and Individualized Approaches

25:48 Introduction to DreamSeq Study

27:00 Demographics and Treatment Regimens

28:56 Discussion on Figures: Webergram and Rebogram

30:43 Impact of Trial Design on Treatment

32:02 Underestimating the Benefit of Immunotherapy First Strategy