Paper details:

BIOL-L104 students,

Attached are the New England Journal of Medicine article “Improved Survival with Vermurafenib in Melanoma with BRAF V600E Mutation” and the Supplementary Appendix for that article. That article reports results of the trial that the two cousins with melanoma participated in.
[Note: “Vemurafenib” is a different name for “PLX4032.”]

Part A: About the abstract, on page 2507:

1. Do your best to translate this statement into your own words: “At 6 months, overall survival was 84% (95% confidence interval [CI], 78 – 89) in the vemurafenib group.”

2. The abstract says that “Response rates were 48% for vemurafenib and 5% for decarbazine.” What is the meaning of “response rate,” here? [Here’s a biig clue: the authors are referring to the RECIST meaning of “response.”]
—–

Part B: About the Supplementary Figure: “Disposition of patients accrued to BRIM,” on the final page of the Supplementary Appendix:
[Note: The legend for that figure is on the page before the figure itself.]

1. How many subjects are in the intention-to-treat Vemurafenib group, and how many subjects are in the intention-to-treat Decarbazine group?
[Note: Although we discussed extremely briefly “intention-to-treat” analysis in class, you may want to look up that term. Here are two resources about it: < https://en.wikipedia.org/wiki/Intention-to-treat_analysis > and < http://aphasiology.pitt.edu/archive/00000188/01/23-05.pdf >.]

2. Based on this figure, does it look as though subjects who refuse treatment are allowed to remain in the trial? Explain.

3. What appears to be the main reason why patients who were screened were not admitted into the trial?
—–

Part C: Panel A of Figure 1: “Overall Survival,” on page 2511:

1. How many subjects were in the Decarbazine group, and how many subjects were in the Vemurafenib group?

2. Is it possible to tell from this figure how many subjects died in the Decarbazine group and how many died in the Vemurafenib group? If so, how many such deaths were there in each group?

3. What would you estimate to be the Kaplan-Meier estimate of the median time to death A) for the Decarbazine group, and B) for the Vemurafenib group? [And, yes, I did intentionally use the term “estimate” twice, here.]

4. Why is there such a dramatic, sudden drop off of % alive between 10 and 11 months? (Presumably it wasn’t the case that tons of subjects died at the same, specific time. So, why the sudden drop off?)

5. Come up with and explain questions and thoughts (about Panel A of Figure 1).

6. Suppose that the Kaplan-Meier estimate of the % of one group’s subjects who are alive at a particular time point is 85%. Suppose that one subject in that group then dies. What would be the new Kaplan-Meier estimate of the % of subjects in that group who are alive immediately after that death?
[Note: This question isn’t specifically about this figure, but is instead about the general method of determining Kaplan-Meier estimates.]
—–

Part D: Panel A of Figure 2: “Progression-free Survival,” on page 2512

1. What does “progression” mean? (Big hint: It’s the meaning used in RECIST guidelines.)

2. How many subjects were in the Decarbazine group, and how many subjects were in the Vemurafenib group?

3. Why do you suppose that the numbers of subjects in Panel A of this figure are different from those in Panel A of Figure 1?

4. How often does it seem as though tumors were supposed to be measured? Why do you say so?

5. Why do you suppose that the two curves have a sort of wavy or step-like appearance (with periodic, sudden vertical drops in %)? (What might be an explanation for that?)

6. What would you estimate to be the Kaplan-Meier estimate of the median time to progression or death A) for the Vemurafenib group, and B) for the Decarbazine group?

7. Suppose that a subject’s tumors are measured and are judged to have not yet reached progression. Suppose that this subject dies before the tumors are measured again. Would that person’s death change the Progression-free Survival %? Explain.
—–

Part E: Figure 3: “Best Tumor Response for Each Patient,” on page 2513:

1. Why do you suppose that the numbers of subjects in this figure are different from those in Panel A of Figure 2?

2. Based on a quick glance at this figure, roughly what percentage of subjects seem to have had a RECIST Response A) in the Vermurafenib group, and B) in the Decarbazine group?
—–

Part F:

As time permits, come up with and explain additional questions and thoughts about this article.
Prof.
[see attachment: “Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation.pdf”, size: 582180 bytes]
[see attachment: “Supplementary Appendix.ImprovedSurvivalVemurafenib.pdf”, size: 66314 bytes]
Client:
plz answer the question

Paper details:

BIOL-L104 students,

Attached are the New England Journal of Medicine article “Improved Survival with Vermurafenib in Melanoma with BRAF V600E Mutation” and the Supplementary Appendix for that article. That article reports results of the trial that the two cousins with melanoma participated in.
[Note: “Vemurafenib” is a different name for “PLX4032.”]

Part A: About the abstract, on page 2507:

1. Do your best to translate this statement into your own words: “At 6 months, overall survival was 84% (95% confidence interval [CI], 78 – 89) in the vemurafenib group.”

2. The abstract says that “Response rates were 48% for vemurafenib and 5% for decarbazine.” What is the meaning of “response rate,” here? [Here’s a biig clue: the authors are referring to the RECIST meaning of “response.”]
—–

Part B: About the Supplementary Figure: “Disposition of patients accrued to BRIM,” on the final page of the Supplementary Appendix:
[Note: The legend for that figure is on the page before the figure itself.]

1. How many subjects are in the intention-to-treat Vemurafenib group, and how many subjects are in the intention-to-treat Decarbazine group?
[Note: Although we discussed extremely briefly “intention-to-treat” analysis in class, you may want to look up that term. Here are two resources about it: < https://en.wikipedia.org/wiki/Intention-to-treat_analysis > and < http://aphasiology.pitt.edu/archive/00000188/01/23-05.pdf >.]

2. Based on this figure, does it look as though subjects who refuse treatment are allowed to remain in the trial? Explain.

3. What appears to be the main reason why patients who were screened were not admitted into the trial?
—–

Part C: Panel A of Figure 1: “Overall Survival,” on page 2511:

1. How many subjects were in the Decarbazine group, and how many subjects were in the Vemurafenib group?

2. Is it possible to tell from this figure how many subjects died in the Decarbazine group and how many died in the Vemurafenib group? If so, how many such deaths were there in each group?

3. What would you estimate to be the Kaplan-Meier estimate of the median time to death A) for the Decarbazine group, and B) for the Vemurafenib group? [And, yes, I did intentionally use the term “estimate” twice, here.]

4. Why is there such a dramatic, sudden drop off of % alive between 10 and 11 months? (Presumably it wasn’t the case that tons of subjects died at the same, specific time. So, why the sudden drop off?)

5. Come up with and explain questions and thoughts (about Panel A of Figure 1).

6. Suppose that the Kaplan-Meier estimate of the % of one group’s subjects who are alive at a particular time point is 85%. Suppose that one subject in that group then dies. What would be the new Kaplan-Meier estimate of the % of subjects in that group who are alive immediately after that death?
[Note: This question isn’t specifically about this figure, but is instead about the general method of determining Kaplan-Meier estimates.]
—–

Part D: Panel A of Figure 2: “Progression-free Survival,” on page 2512

1. What does “progression” mean? (Big hint: It’s the meaning used in RECIST guidelines.)

2. How many subjects were in the Decarbazine group, and how many subjects were in the Vemurafenib group?

3. Why do you suppose that the numbers of subjects in Panel A of this figure are different from those in Panel A of Figure 1?

4. How often does it seem as though tumors were supposed to be measured? Why do you say so?

5. Why do you suppose that the two curves have a sort of wavy or step-like appearance (with periodic, sudden vertical drops in %)? (What might be an explanation for that?)

6. What would you estimate to be the Kaplan-Meier estimate of the median time to progression or death A) for the Vemurafenib group, and B) for the Decarbazine group?

7. Suppose that a subject’s tumors are measured and are judged to have not yet reached progression. Suppose that this subject dies before the tumors are measured again. Would that person’s death change the Progression-free Survival %? Explain.
—–

Part E: Figure 3: “Best Tumor Response for Each Patient,” on page 2513:

1. Why do you suppose that the numbers of subjects in this figure are different from those in Panel A of Figure 2?

2. Based on a quick glance at this figure, roughly what percentage of subjects seem to have had a RECIST Response A) in the Vermurafenib group, and B) in the Decarbazine group?
—–

Part F:

As time permits, come up with and explain additional questions and thoughts about this article.
Prof.
[see attachment: “Improved Survival with Vemurafenib in Melanoma with BRAF V600E Mutation.pdf”, size: 582180 bytes]
[see attachment: “Supplementary Appendix.ImprovedSurvivalVemurafenib.pdf”, size: 66314 bytes]
Client:
plz answer the question