A VIDEO RECORDING OF THIS INTERVIEW IS AVAILABLE HERE.

This time, we look to New York for guidance on recognizing and treating monkeypox.

Dr. Eric Meyerowitz of Montefiore and Dr. Stephen Baum of Einstein will lead you through the monkeypox thicket in a 17-minute chat.

Included below is information for patients as well as links to some key articles of interest to clinicians.

LINKS:

For patients: Dr. Barry Zingman’s “Monkeypox — What you need to know”

For clinicians:

A VIDEO RECORDING OF THIS INTERVIEW IS AVAILABLE HERE.

We’re back with another interview from this year’s IASLC conference.

This time, Christine Sadlowski and Dr. Julia Rotow interview Dr. Mariano Provencio about the survival outcomes from the NADIM II trial. In that trial, patients with resectable stage III AB non-small cell lung cancer received nivolumab plus chemotherapy versus chemotherapy alone.

Overall survival at 5 years in these patients has been roughly 30%, according to Provencio. With the addition of chemo-immunotherapy, patients who showed a complete pathological response were all alive at the 3-year mark. These results, according to Rotow, are “really quite exciting.”

INTERVIEW TRANSCRIPT

Christine Sadlowski:

This is part of the NEJM Group coverage of the IASLC’s 2022 World Conference on Lung Cancer. I’m Christine Sadlowski, and with me Dr. Julia Rotow, a clinical oncologist at Dana-Farber Cancer Institute in Boston. We’re here to interview Dr. Mariano Provencio, Chair of Medical Oncology at the Hospital Universitario Puerta de Hierro Majadahonda in Madrid in Spain. He is the lead author on NADIM II, a phase 2 trial of neoadjuvant nivolumab added to chemotherapy for resectable stage III AB non-small cell lung cancer. Welcome.

Dr. Mariano Provencio:

Thank you.

Christine Sadlowski:

So first, I’d like to ask you about the history of this research because these findings come after several previous studies, including NADIM nivolumab in this clinical setting. Can you refresh us briefly on what is known so far?

Dr. Mariano Provencio:

We studied the combination with nivolumab plus chemotherapy in NADIM I. It was a clinical trial focused on stage IIIA according to the 7th edition. It was a phase two trial. We obtained very exciting results: in overall survival, three times the historical series; in DFS [disease-free survival] around 77 percent at two years — almost double the historical series — and also early results in PCR, pathological complete response, almost 60 percent.

Then following that was the second clinical trial comparing nivolumab plus chemotherapy versus chemotherapy, and this is NADIM II.

Dr. Julia Rotow:

Thank you, Dr. Provencio. So, when you think about what we knew already in the field, could you take us through some of the key findings from the NADIM II study and what these might add to our current understanding of nivolumab in this setting?

Dr. Mariano Provencio:

In NADIM II, the primary objective was complete pathological response, and we obtained higher complete pathological response in the experimental arm. Nivo plus chemo versus chemo: Odds Ratio 7.88; p = 0.0068. We presented at the last lung cancer congress (IASLC) more progress, in PFS longer with hazard ratio of 0.48 and more overall survival hazard ratio of 0.40. And this is quite amazing results, in my opinion, comparing with chemotherapy arm.

Christine Sadlowski:

Can I go back a little bit and say in this particular presentation you’re showing primarily secondary outcomes, is that correct?

Dr. Mariano Provencio:

We presented the primary end point was a complete pathological response. It was positive and then we presented in this congress the secondary outcomes, survival outcomes, yes.

Christine Sadlowski:

And they were at 12 and 24 months, correct?

Dr. Mariano Provencio:

Correct.

Christine Sadlowski:

I was struck by the finding on overall survival. That’s obviously improved with adjuvant therapy.

Dr. Mariano Provencio:

We use adjuvant nivolumab therapy for six months. We think so, this is the first clinical trials who reported an increase in overall survival in this setting using immunotherapy plus chemotherapy and adjuvant.

Dr. Julia Rotow:

I was struck by these results. They were quite impressive. Are there any caveats we should take away from your status as secondary versus primary outcomes on the study?

Dr. Mariano Provencio:

In the first clinical trial, in NADIM I, the primary endpoint was progression-free survival. We saw pathological complete response was quite robust endpoint. I think these results are very significant in survival outcomes are very, very significant.

Christine Sadlowski:

So, what does that mean for clinical practice? I don’t actually know how nivolumab is currently used. I understand it’s approved for other cancers, not this one, but is it currently used?

Dr. Mariano Provencio:

Currently, we are using a chemo and then certainly in some cases immunotherapy, this subgroup of patients in stages 3A-B (N2) disease have poor prognostic and based on our results we can improve it. We have had the same results during last 30 years using chemotherapy and then these results are quite similar than the CM 816 specifically in stage 3A 3B. In some cases, these patients are considered with unresectable disease, and we obtain very high rate of surgery in these patients, more than 90 percent of patients underwent radical surgery is quite important to the clinical practice, in my opinion.

Our opinion, we should use chemo plus immunotherapy as standard of care in this group of patients as in the adjuvant setting.

Dr. Julia Rotow

You mentioned Checkmate 816, and I know this regimen involves a longer course of immunotherapy because of the adjuvant period. Is there anything that clinicians or patients should know about adverse effects that you saw with this regimen?

Dr. Mariano Provencio:

I think both trials are quite well tolerated results. In CM 816 we don’t use adjuvant therapy. I think maybe we have to have more results, more information about adjuvant period or adjuvant after chemo immunotherapy. Maybe in the future we’ll have to define with more detail this aspect. In any case, I think the most important part is use neoadjuvant chemo immunotherapy.

Dr. Julia Rotow:

I thought that it was great that you highlighted the surgical resection rate because it was quite a bit better with the combination chemo immunotherapy.

Dr. Mariano Provencio:

We have more than 92 percent of surgery. I mentioned before 70 percent of patients had N2 affectation. Half of them, multiple station. This is quite a high rate of radical surgery on more than 92 percent of R0 versus 60 percent in control arm. I think the surgery could be an important aspect to cure these patients.

Christine Sadlowski:

What would you need to do next to show that?

Dr. Mariano Provencio:

The next steps in this case, I think now this is a proof of concept introducing a new treatment in this group of patients. Very important this group of patients. We have almost the same survival within the last 30 years. Around 30 percent of overall survival at five years and no more than 12 or 16 months PFS. I think we have to analyze with more detail clinical trials analyzing pathological response and then in this case adjuvant treatment in these patients according to pathological response.

For example, in our study patients with PCR (complete pathological response) are 100 percent of disease-free and 100% alive at three years.

Dr. Julia Rotow:

Thank you for taking us through. I agree these are really quite exciting results and we’re so happy to have gotten to see them at the conference this year. We certainly look forward to seeing more of this sort of treatment strategy. So, thank you for joining us today.

Dr. Mariano Provencio:

Thank you.

Christine Sadlowski:

Thank you.

A VIDEO RECORDING OF THIS INTERVIEW IS AVAILABLE HERE.

Interim results on overall survival in phase 3 of the IMpower010 trial were presented at this year’s meeting of the International Assosciation for the Study of Lung Cancer (IASLC). As part of the NEJM Group’s coverage of the conference, Christine Sadlowski interviewed the presenter, Dr. Enriqueta Felip. In a 15-minute interview, she discusses the implications for different patient groups and the past, present, and future of the IMpower trial, which tests adjuvant atezolizumab following platinum-based chemotherapy in patients with resected early-stage non–small-cell lung cancer. 

INTERVIEW TRANSCRIPT:

Christine Sadlowski:

This is coverage of the IASLC’s 2022 World Conference on Lung Cancer. I’m Christine Sadlowski of the NEJM Group. With me today is Dr. Enriqueta Felip, who is head of the thoracic cancer unit at the Vall d’Hebron University Hospital, Vall d’Hebron Institute of Oncology in Barcelona, Spain. She is the presenting author for the overall survival interim analysis of IMpower010, which tested atezolizumab in patients with resected early stage non-small cell lung cancer following platinum-based chemotherapy.

Dr. Felip, thank you very much for joining me.

Dr. Enriqueta Felip:

Thank you. It’s a pleasure.

Christine Sadlowski:

So, last year I interviewed your colleague, Dr. Heather Wakelee, about the interim findings on progression-free survival from this same study. Can you briefly remind us what those findings were?

Dr. Enriqueta Felip:

So, IMpower010 is a randomized trial in patients with completely resected stage IB with a tumor size greater than four centimeters, II-IIIA according to the Seven TNM Classification, and patients received adjuvants, platinum-based chemotherapy, and then 1,000 patients were randomized to receive one year of atezolizumab or best supportive care. The primary endpoint in this trial was the disease-free survival, and the primary endpoint was presented by Dr. Wakelee during the ASCO last year and also published in Lancet.

So, in this trial, for those patients with stage II-IIIA and PD-L1-positive tumors, atezolizumab improved disease-free survival with a hazard ratio of 0.66. For those patients with stage II-IIIA, irrespective of PDL-1, disease-free survival was improved with a hazard ratio of 0.79, and in the whole group of patients, patients with a stage IB-IIIA, the hazard ratio for disease-free survival was 0.81, and the statistical significance boundary for disease-free survival was not met in this population.

So here, during the IASLC conference, we present the first prespecified interim analysis of overall survival and a safety analysis with a median follow-up of 45 months and with a clinical cutoff in April 2022. So, at this analysis with an event to patient ratio of 25% in the intention-to-treat population, the overall survival is not mature.

So, in this analysis, we presented the results of overall survival in this interim analysis for patients with stage II-IIIA and PD-L1-positive tumors. Overall, there is a trend towards an improvement in overall survival for those patients receiving atezolizumab. The median overall survival was not reached in either of the treatment arms. The hazard ratio was 0.71 with a 95% confidence interval between 0.49 to 1.03. So, at 60 months there is 76.8% of the patients alive in the atezolizumab arm, 67.5% of the patients in the control arm.

At this overall survival interim analysis, we observe no differences in overall survival when we analyze all randomized stage II-IIIA population, irrespective of PD-L1, with a hazard ratio of 0.95, and also no differences in overall survival was observed in an intention-to-treat population, including patients with a stage IB disease, with a hazard ratio of 0.995.

And also, we analyzed the overall survival in patients with stage II-IIIA based on PD-L1. So, as I mentioned, for those patients with PD-L1-positive tumors, there is a nonsignificant trend in favor of atezolizumab with a hazard ratio of 0.71. For those patients with PD-L1-negative tumors, the hazard ratio is 1.36, and for those patients with PD-L1 50% or higher, the hazard ratio for overall survival is 0.43. We analyzed also the hazard ratio for those patients with PD-L1 between 1-49%, that is 0.95. So, it’s important that for those patients with PD-L1 50% or higher, when we exclude those patients with EGFR and ALK, the hazard ratio for overall survival is 0.42, the median overall survival was not reached in both treatment arms, and at five years, there are 84% of the patients in the atezolizumab arm, 67% in the control arm.

I think it’s also important that we have updated the safety profile in this new data cutoff. Overall, the safety profile was consistent with the previous analysis and no new safety signals were seen.

So, what we have seen in this presentation is that we have observed an overall survival trend in favor of atezolizumab in those patients with stage II-IIIA and PD-L1-positive tumors. The hazard ratio is 0.71, 91% confidence interval between 0.49-1.03. For those patients with PD-L1 50% or higher and a stage II-IIIA, the overall survival hazard ratio is 0.43. After additional follow-up, the safety profile remains the same, no unexpected safety signals, and we will continue to the final disease-free survival analysis, and also with further overall survival follow-up.

Christine Sadlowski:

What is the distinction between the patients with PD-L1 1% or greater versus those with 50% or greater? I understand the drug has actually been approved through those two different populations. In the United States and some other countries, it’s approved for those with 1% or greater versus Europe, it’s 50% or greater. Why the difference?

Dr. Enriqueta Felip:

Yeah. The approval of atezolizumab in the adjuvant setting was based on the disease-free survival, published and presented at ASCO. As you mentioned, there are two different approvals. In the United States, the approval is in patients with PD-L1-postive stage II-IIIA, and in Europe, it’s for those patients with stage II-IIIA, PD-L1 50% or higher, excluding those patients with EGFR and ALK.

We have seen that the hazard ratio is different in the two populations, but it’s true that when we presented the prior results, the analysis in patients with PD-L1 between 1-49% was exploratory, so this was not the main endpoint of the trial. So, the trial was hierarchically designed, one, first for patients with stage II-IIIA and PD-L1-positive tumors, then for patients with stage II-IIIA, and if positive, in patients with stage IB-IIIA. The disease-free survival in patients with PD-L1 50% or higher is a secondary endpoint, but the analysis in patients with PD-L1 between 1-49% was a post hoc analysis.

Christine Sadlowski:

So, what is the implication here for those two different populations?

Dr. Enriqueta Felip:

I think this is the first time in the adjuvant setting, this was the first study with results. We have also now the KEYNOTE-091, presented also in ESMO Plenary, showing that adjuvant immunotherapy improves disease-free survival in patients with completely resected and stage II-IIIA.

In my opinion, the results are clear for patients with PD-L1 50% or higher, but even for those patients with PD-L1 between 1-49%, we cannot exclude a benefit. So, as I mentioned, this is a post hoc analysis, so probably we need to individualize the treatment in this group of patients with stage II-IIIA and PD-L1 between 1-49%.

What we have seen in the cohort is no benefit of adjuvant immunotherapy for those patients with PD-L1-negative tumors.

Christine Sadlowski:

So, what is the timing for the remainder of this overall survival analysis?

Dr. Enriqueta Felip:

Yeah. So, during this meeting, we have updated the overall survival as prespecified in the first interim analysis. There are remaining other analyses of overall survival in the future, and we have not updated the disease-free survival. So, this is important, there are not enough events for the final disease-free survival analysis, and we calculate that we will have these events probably late 2023.

Christine Sadlowski:

So, overall you’d say these are still very positive findings, right?

Dr. Enriqueta Felip:

Yes. I think so. So, for patients with stage II-IIIA, the hazard ratio for disease-free survival is 0.66 in PD-L1-positive tumors. For overall survival, I mentioned there is a trend that is not statistically significant, but we have in this group of patients a hazard ratio for overall survival of 0.71, and we analyzed the patients with PD-L1 50% or higher, the hazard ratio for disease-free survival and overall survival is 0.43.

I have to say that according to the statistical design, you know, the study has a hierarchical design, so to formally test the overall survival, we need to have a positive disease-free survival results in the intention-to-treat population, and this is not happening with the present analysis, but overall, I think these are positive findings in patients with early-stage disease.

Christine Sadlowski:

What would you tell your patients at this point? They are receiving this treatment now, right? What do you tell them about this?

Dr. Enriqueta Felip:

No. I think we need to test for PD-L1, also early-stage of disease specimens. I think testing is important, not only for PD-L1, but also probably for EGFR and ALK in this scenario, patients with resected tumors, and I think we need to discuss with our patients these results, the hazard ratio of 0.43 for disease-free survival in PD-L1 50% or higher, and also, as I mentioned, probably to individualize the treatment for those patients with resected stage II-IIIA and PD-L1 between 1-49%.

Probably, it’s not the same, a patient with a PD-L1 of 40% or a patient with a PD-L1 1%, so there are a number of…also, we need to analyze the possibility of disease recurrence in each individual case in this group, that are those patients with PD-L1 between 1-49% and pathologically stage II-IIIA.

Christine Sadlowski:

Is there anything else you think clinicians should know about this?

Dr. Enriqueta Felip:

I think immunotherapy, this is one trial. As I mentioned, the results presented of KEYNOTE-091, and importantly, we have also results with neoadjuvant strategies.

So, CheckMate 816 is a trial published in the New England Journal of Medicine in patients that perhaps are slightly different because the patients are clinically staged. So, in our trial, in IMpower, the patients were included with pathological staging after surgery. In the CheckMate 816, patients were included with clinical staging before surgery, but it’s also an important trial showing that preoperative chemo plus immunotherapy improves, increases the number of pathological complete responses and also is associated with longer event-free survival.

Probably the situation is that the CheckMate 816, I think 60% of the patients included had the stage IIIA disease that was, as I discussed, diagnosed pre-surgery, but you know, overall, we are seeing that immunotherapy will be part of the treatment of patients with early-stage disease, probably excluding those patients with EGFR and ALK, and we’ll have also positive trials with neoadjuvant strategies and with adjuvant therapy.

Christine Sadlowski:

Thank you very much.

Dr. Enriqueta Felip:

Thank you. Thank you, Christine.

A VIDEO RECORDING OF THIS INTERVIEW IS AVAILABLE AT THIS LINK.

In treating most exacerbations of chronic obstructive pulmonary disease (COPD) the usual regimen consists of prednisone plus 5- to 7-days of antibiotics. But what if a shorter course of antibiotic therapy would do? That would be both convenient for patients and less likely to promote antibiotic resistance.

A recent paper in Therapeutic Advances in Respiratory Disease describes just such a strategy: patients received prednisone plus either 2 or 7 days of levofloxacin. There was no substantive difference in clinical results between the groups. Summarized in NEJM Journal Watch General Medicine as “practice changing,” this research seems worth a closer look.

To that end we’ve invited two of the researchers and the Journal Watch editor who wrote the summary to discuss the issues raised.

Have a listen to this 14-minute Clinical Conversation.

(A note of no great consequence: We’ve called this “Podcast 298” because, while numbering the titles, your host negligently skipped from 297 to 299 in his haste to achieve 300 episodes.)

Therapeutic Advances in Respiratory Disease paper

Journal Watch summary

TRANSCRIPT

Joe Elia:

A recent summary in NEJM Journal Watch Journal General Medicine labeled a study about treating acute exacerbations of chronic obstructive pulmonary disease — or COPD — as practice changing, so it seems important to spread the news.

To do that, we’ve got Dr. Daniel Dressler, the summarizer of the study, Dr. Salma Messous, the study’s first author, and Dr. Semir Nouira, a senior author, to discuss it with us.

Dr. Dressler is a professor of medicine at Emory University in Atlanta. He is also deputy editor of NEJM Journal Watch General Medicine. Dr. Messous and Dr. Nouira are in the Emergency Department and the Department of Laboratory Research at Monastir University in Tunisia. Welcome to you both.

Dr. Semir Nouira: 

Thank you very much. Welcome.

Dr. Salma Messous:

Thank you very much.

Dr. Daniel Dressler: 

Thank you so much, Joe. Welcome, again, to Dr. Messous and Dr. Nouira.

I’ll just jump in and ask you if you would agree with this thumbnail description of your work: You randomized approximately 300 patients with acute exacerbation of COPD to one of two antibiotic regimens, either a two-day course of levofloxacin — or a seven-day course, which is the usual care, so I’ll ask you if that’s correct and if you can tell us briefly why you undertook this study, and essentially what you found.

Dr. Semir Nouira:

Thank you, Dan, for your choice of our study. I’m very proud to be here and to be with you to explain the background of our study and the results of our study.

Our study is probably the first that compares a short course of antibiotic — as short as two days — compared to seven days’ conventional duration. We found that there are similar results, and that the two-day is as effective as seven days.

You know, actually the objective of the study is not to show or to demonstrate the similarity between short course and conventional course of antibiotics, this was clearly shown many years ago — I can say at least since 2008, since the publication of the first analyses comparing the efficacy between short and a conventional course. So years ago it was shown, this evidence.

This was not our question, and as you can expect, this is very important as a result to know, it’s very important, it’s very relevant because this would lead to less consumption of antibiotics, less antibacterial resistance, less adverse effects, and perhaps more compliance.

So this was demonstrated many years ago, but the question of the present study is the following: What is the shortest course of antibiotics that we can accept for our patient, COPD patients with exacerbation. This is the main question of the study, and you know that according to a recent recommendation of the GOLD, it is recommended that antibiotic therapy should not exceed five days, and some studies demonstrate that even with three days, we can have similar results as conventional duration. So for us, the question is, could we decrease the duration to less than three days? And that’s why we performed this study because according to in vitro and animal studies, antibiotic therapy has its maximum effect during the first hours, so why not reduce antibiotic therapy to the least duration?

This was the background of our study, and fortunately, we demonstrate that we had similar clinical outcome with respect to clinical cure, to the need for additional antibiotic therapy, to the need for ICU admission, and to the duration of the exacerbation-free interval. So this is the background of our study, and these are the main findings of our study.

Joe Elia: 

I wanted to ask you, Dr. Dressler, why you consider the research practice-changing or potentially so. Is the 5- to 7-day regimen baked into the current guidelines here?

Dr. Daniel Dressler:

Sure, and thank you, Dr. Nouira for that answer and response.

I also appreciate that there have been maybe some other studies that have suggested shortening the course for COPD is probably appropriate, and yeah, still the GOLD guidelines or the international guidelines for management of COPD and COPD exacerbation still are recommending even in 2022 this 5- to 7- day course of antibiotics, and so I applaud you for what you’ve done, which is trying to see, well, can we get even shorter than the 5 days, even shorter than a 3 day course. I think that you were able to demonstrate that in your patient population the equivalence in outcomes even with a 2- day course compared to a 7-day course, and so I find that really valuable, really impressive. And you say it can also really help clinicians feel comfortable that they can actually shorten the course. Maybe it will impact or influence guidelines in the future to help maybe suggest a shorter course. So I think that is why I consider it a value-added piece of medical literature and clinical literature, and something that we can practice on and maybe practice changing for many clinicians.

Joe Elia: 

You also noted in your comment, Dr. Dressler, that the findings need to be confirmed and more work needs to be done in this area, but I can see the advantage of having a patient only taking two days and not trying to take a seven-day course.

Dr. Messous, your design was practical in nature. By that I mean, some patients remained in the hospital even while on the two-day course if it was considered clinically prudent to do so, and of course, everyone received prednisone intravenously or by mouth, if they were at home. Do you think you’ve got enough data to recommend two-day regimen as routine, and do your hospitals use the two-day regimen now?

Dr. Salma Messous:

So, it’s a bit early to make recommendations. We need larger studies. This may allow us to better target our recommendations for the duration of antibiotic therapy, for example, according to their age, the existence of pulmonary edema, comorbidity, biomarkers, et cetera. So maybe Professor Nouira can add a comment regarding this question.

Dr. Semir Nouira:

Thank you, Salma, for your answer. What I can add as to whether there is enough data to recommend two-day regimen as routine treatment, the answer, of course, is no, because I think there’s not enough data for that. With the available evidence, we can’t recommend two days, but in my opinion, there are two recommendations and two directions for future investigation.

First, we must have more investigation to select patients who need antibiotics for COPD exacerbation. This is the first step, and it’s a big challenge now. It’s very widespread to give antibiotics, and unfortunately, until now, we don’t know the best profile of patients who really need antibiotics, so this is the first step.

The second step and the second direction, once the first step is clearly answered, is to try to know what is the optimal duration of the antibiotic course. I think it can be two days. It can be more. It can be less. It probably depends, as said by Salma, on the patients. Probably we will recommend antibiotic duration according to the patient’s characteristics, biomarkers or clinical characteristics such as age, sex, or comorbidities or something like that. So I think it’s really early to recommend a two-day antibiotic therapy for acute exacerbation of COPD.

Dr. Daniel Dressler:

Thank you for those answers to Joe’s questions.

I will say also that I’m glad you brought up patient population and determining which patients need antibiotics at all for COPD exacerbation. I think you all did a nice job in trying to identify those patients and not including patients that did not meet the sort Anthonisen criteria for requiring antibiotic therapy or potentially needing antibiotic therapy, so I appreciate that, and because we have other data that suggests that, potentially, patients with COPD exacerbation that are low risk, you know, whether or not they need antibiotics at all, you may be getting to some of that. I think your study did a very nice job even with only about 300 patients and it’s still comparable to many studies in COPD in terms of size, and so I appreciate the work that you all have done.

I’m wondering what has been the reaction of your colleagues related to this research and these outcomes that you found?

Dr. Semir Nouira:

You know, it’s a very big challenge to translate scientific results into clinical practice, it’s not easy at all, even in the developed countries — and the examples are numerous. You know, despite the evidence that a short course of antibiotics is as effective as conventional course, I think more than half of the physicians continue to prescribe antibiotic for at least seven days, and this is evident, so it’s a very big change, and for the Tunisian physician, it’s the same issue, of course — there’s no reason to be different, you know.

Perhaps, we need to do more to make our results more visible, so it’s the future of our effort. We must not limit ourselves to recommendation, but we must follow this recommendation and try to translate these recommendations into clinical practice, and this is our job.

Dr. Daniel Dressler:

Greatly appreciated, as well, and hopefully, we’re helping do something with you.

Joe Elia:

I want to thank you, Dr. Messous and Dr. Nouira, and Dr. Dressler for this chat today.

Dr. Semir Nouira:

Thank you, Joe.

Dr. Salma Messous:

Thank you, Joe, very much.

Dr. Semir Nouira:

Thank you very much, Dan.

Joe Elia: 

We will call that the 298th edition of clinical conversations all of which are available free at podcasts.jwatch.org. We come to you from the writers and editors of the NEJM Group. Our executive producer is Kristin Kelley, and I’m Joe Elia. Thanks for listening.

A VIDEO RECORDING OF THIS INTERVIEW IS AVAILABLE HERE.

THE USUAL AUDIO FILE IS AVAILABLE BELOW

Steven Cummings has co-written a take-no-prisoners editorial in the New England Journal of Medicine. The topic? Vitamin D supplements. The conclusion? “…providers should stop screening for 25-hydroxyvitamin D levels or recommending vitamin D supplements, and people should stop taking vitamin D supplements to prevent major diseases or extend life.”

Dr. Cummings was commenting on research findings from the VITAL trial, also published in the journal, showing no fracture-lowering benefits of the supplements.

Allan Brett interviews Cummings to get the details on his pronouncement, and it takes just 13 minutes to dismiss vitamin D (which, by the way, is not a vitamin at all).

NEJM presentation of VITAL results

Cummings and Rosen editorial

A VIDEO RECORDING OF THIS ROUNDTABLE IS AVAILABLE CLICK HERE.

THE USUAL AUDIO FILE IS AVAILABLE BELOW

Your host is old enough to remember when hospital corridors featured physicians with little black bags, scurrying around to see their patients.

That’s no longer true, of course. Most of the physicians seen in those corridors these days are white-coated employees.

The Annals of Internal Medicine reported a few months ago that “By 2018, 71% of newly certified general internists practiced as hospitalists, compared with only 8% practicing as outpatient-only physicians.”  In addition, between 2008 and 2018 mixed-practice physicians — those black-bag-carrying types — declined by over 50%.

To investigate this shift, we gathered five young internists for a roundtable discussion on the attractions of the hospitalist specialty.

Running time: 30 minutes

Annals of Internal Medicine article

CREST-2’s results are probably more than a year away. In the meantime, what to do about diagnosed severe (but asymptomatic) carotid stenosis? Recent results suggest that medical management compares favorably with the surgical approach.

In this edition, we address the question with a conversation between Dr. Allan Brett, NEJM Journal Watch‘s editor-in-chief, and Dr. Seemant Chaturvedi, a University of Maryland neurologist who serves on CREST-2’s executive committee.

[Running time: 16 minutes]

NEJM Journal Watch coverage of a recent JAMA paper on the topic.

Locally advanced rectal cancer usually receives a three-part treatment: chemotherapy followed by radiotherapy and then surgery.

In a small-cohort study presented at this year’s ASCO conference researchers used a PD-1 inhibitor — dostarlimab — every three weeks for 6 months against the disease. All patients had mismatch repair deficient tumors. No other treatments were needed however, since the 12 patients all attained complete response if they completed the regimen.

As part of the NEJM Group’s coverage of ASCO, Christine Sadlowski interviewed the study’s first author, Dr. Andrea Cercek of Memorial Sloan Kettering Cancer Centern about the study and its implications.

The study as published in the New England Journal of Medicine

Patients with metastatic breast cancer whose tumors express low levels of HER2 are generally classified and treated as having HER2-negative disease.

However, Dr. Shanu Modi of the Memorial Sloan Kettering Cancer Center and a group of international collaborators explored the use of a monoclonal antibody–drug conjugate (trastuzumab–deruxtecan) in patients with disease they classify as HER2-“low.” Compared with “low” patients treated with one of several standard-of-care regimens, those receiving the conjugate therapy had greater median progression-free survival (roughly 10 months versus 5) and a longer overall survival (roughly 24 versus 18 months).

Christine Sadlowski of the NEJM Group interviewed Dr. Modi during the Group’s coverage of this year’s ASCO meeting, where Modi presented her results.

Have a listen.

Modi et al. as published in the New England Journal of Medicine.

Apnea testing is part of the protocol used to determine whether a patient is dead according to neurologic criteria. The question is, do clinicians need to obtain consent to proceed?

In a fascinating 15-minute chat, two intensivists, Drs. Patricia Kritek and Robert Truog, discuss that question and another, larger one: what is death, anyway? Their back-and-forth was prompted by a recent debate, published in Chest, between two others —  a clinician and a law professor.

Have a listen, and please leave a comment to help guide future editions.

The Chest article

The New Yorker article mentioned by Dr. Truog