Journal Club ft. NEJM publications   

Are there any circumstances where use of T-DXd would supercede the use of CDK4/6 inhibitors or other non-chemotherapeutic options (PIK3CA etc?)

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

PFS curves appear similar between the AKT-altered vs overall study population in the trial publication. Is there any additional information available ...

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...

Given the results of DESTINY-Breast03, and T-DXd's labeled indication in second-line, what is now the role of TDM1 in the treatment armamentarium of H...

Are there other mutations/biomarkers in CLL which may specifically predict for response or resistance to pirtobrutinib?

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

Patient with stage IV ER+PR+Her2- breast cancer progressed after CDK4/6 inhibitor+AI and then on Elacestrant. Guardant 360 showed ESR1 mutation and PI...

In MONALEESA-2, it appears ~22% of those in the ribcociclib group received a subsequent CDK4/6 inhibitor. What was the rationale and could this have i...

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

Role of capivasertib vs SERD? What factors help you decide?

Are there certain patient subgroups for whom you would use the IO+PARPi? Is there data from DUO-E regarding BRCA status and its potential impact on ...

If yes, would you apply this broadly or reserve the addition of IO to chemotherapy for patients with high-risk histologies (e.g., carcinosarcoma) or o...

Does your decision depend on MMR status? Would you use the same approach for neoadjuvant treatment?In light of relevant trials including RUBY, GY018, ...

DUO-E, GY-018, and RUBY included patients with stage III and IV endometrial cancer WITH measurable disease.Would your decision change based on the mis...

Are there patients for whom you would still reserve IO for salvage/recurrent setting (eg IO + lenvatinib)? Would you base this on MMR status or other ...

How much cumulative prednisone exposure do you tolerate and how many attempts at tapering will you pursue before considering addition of a steroid spa...

Will these results change your practice?

After what interval of sustained remission will you attempt to taper, and will you do so by first widening the dosing interval?

Will you initiate sarilumab as a first steroid sparing agent or will you still pursue a DMARD such as methotrexate before initiating sarilumab? To wha...

Do you universally perform baseline DEXA and Hgb A1C? How often are you obtaining routine labs?

Do you feel the study outcomes are clinically meaningful?

Does active smoking status influence this decision?

The cohort in the study was predominantly white. Do these results highlight significant disparities in COPD care?

If so, would this be a consideration in all patients regardless of active smoking status? FeNO in active smokers has been questioned, could this have ...

Do you see utility in trending serum neurofilament light chain levels or any alternative screening methods beyond MRI to help identify amyloid-related...

Are there patients in whom you would specifically avoid this class of treatments?

Majority of patients on the seminal trial (Gross et al., PMID 36094839) had tumors isolated to head & neck, what was the rationale for this?

Do you base your decision on extent of residual disease?  Does the use of (neo)adjuvant immunotherapy have an impact on surgical site size or he...

Is a placebo-controlled trial anticipated?

Based on CheckMate 577?Is DFS endpoint sufficient to establish SOC or is OS benefit needed?

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...

If borderline resectable, can the TOPAZ regimen be considered for downstaging effects?

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...

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?

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

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...

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?

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

How do you differentiate between olaparib, rucaparib, niraparib, talazoparib?

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

Is the benefit in PROpel driven by BRCA1/2 or ATM mutated tumors vs all comers?

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...

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...

The OncotypeDx score was 51 in this scenario. 

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

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...

Would you continue pembrolizumab? Would you introduce olaparib? If using both, how would you sequence? 

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

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

What about for a patient with complete radiographic response who declines surgical management?

How and when do you plan to perform HER2 testing in patients with NSCLC?

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...

How does trastuzumab deruxtecan compare to other HER2 targeted strategies?

What factors would influence your approach?

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...

Are there differences in outcome among the BRCA mutated subgroup, or others?

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

ADVOCATE trial

In the ADVOCATE trial, patients were not re-dosed with rituximab.

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?

For example in a patient with a history of PE?

i.e. EGD surveillance for varices?

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

ex. VEGFR2 expression, inflammatory signature, PDL1, etc.

Do you continue atezolizumab alone? Would you avoid anticoagulation?

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

Do you screen even asymptomatic patients?