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

Summary

In this episode of Melanoma Matters, James Larkin and Sapna Patel discuss the RELATIVITY 047 trial, which evaluated the combination of nivolumab and relatlimab in frontline metastatic melanoma. They cover the trial design, response rates, overall survival, toxicity, and the role of PD-L1 expression in treatment decisions. They also explore the potential use of nivolumab and relatlimab in patients with brain metastases. While the combination showed a superior progression-free survival compared to nivolumab monotherapy, it did not demonstrate a significant overall survival benefit. The tolerability profile was better than ipilimumab and nivolumab combination therapy but had more side effects than anti-PD-1 monotherapy.

Keywords

RELATIVITY 047, nivolumab, relatlimab, metastatic melanoma, checkpoint inhibitors, PD-L1 expression, response rates, overall survival, toxicity, brain metastases

Takeaways

The RELATIVITY 047 trial evaluated the combination of nivolumab and relatlimab in frontline metastatic melanoma.

The combination showed a superior progression-free survival compared to nivolumab monotherapy.

There was no significant overall survival benefit observed in the trial.

The tolerability profile of nivolumab and relatlimab was better than ipilimumab and nivolumab combination therapy but had more side effects than anti-PD-1 monotherapy.

PD-L1 expression may play a role in treatment decisions, but its use as a biomarker is still debated.

The efficacy of nivolumab and relatlimab in patients with brain metastases is an area of interest.

Further follow-up and data analysis are needed to fully understand the long-term outcomes of the combination therapy.

Sound Bites

"Relativity 047 was a randomized phase three study for frontline metastatic melanoma using dual checkpoint inhibition."

"Relativity 047 is hitting some marks, but it's missing others. It has a PFS benefit but no OS benefit."

"The CheckMate 067 trial had a sicker population with higher LDH and declining performance status compared to RELA 047."

Chapters

00:00 Introduction and Trial Background

04:47 Comparison with CheckMate 067 and Study Population Differences

09:48 Challenges of Using PD-L1 Expression as a Biomarker

24:19 Fact Check: Citations and Clarifications

In this inaugural episode of Melanoma Matters, hear our what, why, and thank yous. Thank you (luv-u) to our producer big sister (general) Kippy, to David Gedge and The Wedding Present for use of their song "My Favourite Dress," and to the Uromigos duo of Tom & Brian for showing us what is possible.

In Episode 01, Sapna Patel and James Larkin discuss the CheckMate 067 study, a randomized phase three trial for frontline treatment of metastatic melanoma. They highlight the key findings, including improved progression-free survival, overall survival, and objective response rate with the combination of nivolumab and ipilimumab compared to monotherapy. They also discuss the importance of long-term follow-up and the management of toxicities associated with the combination therapy.

Keywords

melanoma, CheckMate 067, frontline treatment, metastatic melanoma, nivolumab, ipilimumab, combination therapy, monotherapy, progression-free survival, overall survival, objective response rate, toxicity

Takeaways

The combination of nivolumab and ipilimumab showed improved outcomes in progression-free survival, overall survival, and objective response rate compared to monotherapy in the CheckMate 067 study.

Long-term follow-up is important to assess the durability of treatment benefits and the development of long-term side effects.

Toxicities associated with combination therapy need to be managed, and treatment-free intervals can be considered without compromising long-term benefits.

Future trials should focus on capturing data on the development of CNS metastasis and melanoma-specific survival.

Viewer questions may be incorporated in future episodes to provide additional insights and engage the audience.

Sound Bites

"CheckMate 067: Frontline treatment of metastatic melanoma with nivolumab and ipilimumab"

"Treatment-free intervals after immune checkpoint inhibitor, particularly the combinations, does not necessarily compromise long-term benefit"

"Numerically, ipilimumab-nivolumab combination fared better in the development of brain metastases compared to anti-PD-1 monotherapy"

Chapters

00:00 Introduction and Background

05:30 CheckMate 067 Study: Improved Outcomes with Combination Therapy

13:01 Comparison with Pembrolizumab Monotherapy