Journal Club ft. NEJM publications   

Questions discussed in this category

Would you obtain baseline PFT on all patients or only selected high risk patients? Would you repeat PFTs regularly or only if clinically symptomatic?&...

Given strong TDXd efficacy in these patients is there a role to use it earlier than 2nd line? How does prior Her2-directed and/or taxane therapy...

If so, what assay would you use in this population? Do we have data on TMB/PDL1 status of long-term survivors?

TOPAZ-1 trial allowed for up to 8 cycles of gem/cis. Were there differences in chemotherapy duration/# cycles between treatment groups? Does use of du...

Is there a difference in efficacy if dose is given later point during the course of therapy?

How would you balance the OS benefit from TOPAZ-1 with the risks of immunotherapy in this or other high-risk populations?

How do you sequence systemic treatment options for in patients with Child's Pugh B (or greater) in context of IMbrave150 and HIMALAYA? When do you in...

Are there factors which would make you more likely to use atezo/bev vs durva/treme vs TKI?

Is data sufficient to adopt this as the new standard of care? Can you comment on the reported regional and race-based variations in outcomes?  ...

Is there a role for using pembrolizumab alone in microsatellite stable endometrial cancer if patients are unable to tolerate lenvatinib?

In the KEYNOTE-775 study, what was the proportion of patients who had a recurrence free interval ≥1 year from platinum-based cytotoxic chemotherapy...

Are there any planned trials to compare lenvatinib + pembrolizumab and platinum-based cytotoxic chemotherapy for advanced or recurrent endometrial can...

Are there specific clinical or social scenarios that would preclude the use of this treatment?

Anecdotally, I have seen more serious IRAEs in patients I'm treating with this regimen than anticipated. Is there higher risk with this drug combinati...

Are there certain patient or disease related factors that would lead you to incorporate lenvatinib + pembrolizumab earlier?

For example, if the primary breast tumor was HER2 IHC 1+, but a metastatic site was HER2 IHC 0, would you still recommend using T-DXd? Will you chang...

Do you have a BMI threshold where you would convert to weight-based dosing over flat dosing? Are certain agents of more or less concern - PD-1, PD-L1,...

Is there evidence that T-DXd crosses the blood-brain barrier?

Prior studies have shown that there can be significant variation between grading pathologists as to which samples are defined as HER2 IHC +1 versus HE...

Do you find the ibPFS endpoint sufficient to change practice for any or all patients, or will you await OS or other data/trials?

Are there any circumstances where use of T-DXd would supercede the use of CDK4/6 inhibitors or other non-chemotherapeutic options?

Specifically, how do you consider T-DXd use in setting of other antibody-drug conjugates (e.g. sacituzumab vedotin)? Are there any special considerati...

Given the FDA approvals for PARP inhibitors and combinations in mCRPC, when do you obtain NGS for mCRPC? Do you have a preferred assay?

If yes, would you directly add olaparib at progression on abiraterone vs waiting to use abi/olaparib at a later line of therapy?

For example, are you more likely to incorporate T-DXd earlier in sequence for 2+ vs 1+? Is there any justification to change our approach in HER2-zer...

What is the cost and accessibility of CYP2C19 gene testing? Does the limited availability of rapid genotyping techniques limit the clinical applicabil...

How do you plan to incorporate the results of the CHANCE-2 trial (Wang et al., PMID 34708996) in your own practice?

Definitions for "high risk" differ by whether patients receive neoadjuvant chemo and across other contemporary studies. Does the change in AJCC stagin...

The FDA recently approved trastuzumab deruxtecan (T-DXd) in the second line setting. Given the results of DESTINY-Breast03, what is now the role of TD...

Recent articles regarding the use of JAK-Inhibition in RA have suggested to avoid in patients with increased CV risk.  However, RA itself is cons...

Given OlympiA trial with olaparib benefit for gBRCA+ patients?What are barriers that you foresee? In your practice who performs mutation testing and w...

For example, would it be appropriate to consider JAK inhibitor therapy as preferable to TNF-alpha inhibitor in patients with heart failure with reduce...

Which regimen is preferred in second line for these patients? What is the efficacy of TDXd vs tucatinib in CNS metastases?    

Does this raise concerns about the efficacy of adjuvant immune checkpoint inhibition? Are any preliminary results from AMBASSADOR (adjuvant pembrolizu...

Although grade 3 toxicity rates were low, ~10.5% experience some degree of ILD, are there strategies to reduce risk before treatment starts? Are ther...

Does this change for PDL1 1-49% vs >50%? Will you be more likely to employ other checkpoint inhibitors before use of HER2 targeting therapy? Or sta...

In subset analyses of OlympiA there seems to be smaller magnitude of benefit among HR+ patients. In your opinion, should adjuvant olabarib be offered ...

Do you think adjuvant nivolumab should be the new standard of care based on current CM274 DFS data? If OS turns out to be no different, will you still...

Is a 3 month delay too long in someone who had postoperative complications?

How does prior chemotherapy, site of disease, and pathological staging inform your decision? How about molecular markers (PD-L1, ctDNA)?

NCCN recommends perioperative FLOT or FOLFOX vs. neoadjuvant chemoRT with Carboplatin/Paclitaxel or FOLFOX.Does CM-577 and the approval of nivolumab p...

Many of the patients on ASCENT trial were heavily pre-treated and require growth factors. With the day 1,8 treatment cycle, is there a way to minimize...

Are there other treatment variations by clinical subsets (eg tumor location, histology, stage II vs III, other biomarkers) seen in CM577 or other data...

CheckMate 577 only included patients with R0 resection.For R1 resections, guidelines suggest observation vs re-resection only.  

How are you thinking about sequencing therapies for these patients (IO vs chemo vs T-Dxd)? Are the data from DESTINY-Lung01 strong enough to warrant e...

Can patients be re-challenged after developing ILD? Is the toxicity seen with T-Dxd a potential barrier to use?  Do you feel the dosing used in...

Given seemingly improved efficacy in ASCENT patients who had less prior treatment, would you consider use after only one prior agent rather than two? ...

Are there specific patient cohorts in whom you will more preferentially use sacituzumab govitecan? Can data from ASCENT be applied to patients with C...

To what degree do you factor in patient preference when choosing among available treatments? Are there features of each regimen that you emphasize in ...

E.g., MPO vs PR3, newly diagnosed vs relapsed, renal involvement. Acknowledge that the ADVOCATE study was not powered to detect these differences, but...

Conversely: In a patient with N2 EGFR+ NSCLC receiving radiation, would you still consider use of osimertinib?

What was the magnitude of benefit for patients with EGFRm NSCLC by stage?  Are you still considering adjuvant osimertinib for patients with earl...

If patients do recur, do you perform these tests on the initial surgical specimen or on tissue from a fresh biopsy (or both?)

Is data available regarding the percentages of patients in each arm who underwent staging PET or the breakdown of CNS imaging modalities?

Are the rates of adjuvant chemotherapy used in ADAURA consistent with real-world practice?

What parameters do you use to decide to treat beyond progression? Is there any efficacy data from this specific study subgroup in IMbrave150?

In light of the SIRveNIB trial results and now IMbrave150, what is the role of intra-arterial therapy now?

Papers discussed in this category

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The New England journal of medicine, 2016-08-04

NEJM Evidence, 2022 Jun 3

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The New England journal of medicine, 2012-11-08

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J Hepatol, 2021 May 26

NEJM Evidence, 2022 June 6

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Cancer, 2019-09-15

N Engl J Med, 2021 Sep 18

The New England journal of medicine, 2018-05-31

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JCO Oncol Pract, 2022 Jan 07

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European urology, 2014-07

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The Lancet. Oncology, 2017-06

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2019-10-10

JAMA Oncol,

Annals of surgery, 2009-05

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2011-05-20

Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2008-01-10

The New England journal of medicine, 2018-07-12

Annals of oncology : official journal of the European Society for Medical Oncology, 2019-08-01

J Thorac Oncol, 2020 Jan 13

J Immunother Cancer, 2019 Jan 21

ESMO Open, 2021 Aug 31

J Clin Oncol, 2021 Aug 03

N. Engl. J. Med.,

JAMA oncology, 2019-06-01

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NEJM Evidence, 2022 Jun 1

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World J Surg, 2019 Apr

J Surg Oncol, 2020 Sep 24

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Ann Rheum Dis, 2016 Oct 03

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Arthritis Rheumatol, 2021 Mar 24

The Lancet. Oncology, 2019-06

J Clin Oncol, 2020 Feb 14

JAMA Netw Open, 2022 Feb 01

J Clin Oncol, 2021 May 03

The Lancet. Oncology, 2018-03

Nature medicine, 2019-01

J Immunother Cancer,

N Engl J Med, 2021 Oct 28

The New England journal of medicine, 2018-07-19

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J. Clin. Oncol., 2018 May 30

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Journal of clinical oncology : official journal of the American Society of Clinical Oncology, 2017-08-01

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J Clin Oncol, 2020 Mar 13

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