ASCO Journal Club&nbsp;&nbsp;&nbsp;

What do you view as the future role for the combination of durvalumab + olaparib + chemotherapy in the management of patients with advanced/recurrent endometrial cancer following the DUO-E trial results?

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 ...

In light of the improved outcomes seen in patients receiving IO +/- olaparib, what role, if any, do you think pelvic radiation still plays in the management of patients with advanced endometrial cancer?

Would you consider offering immunotherapy +/- olaparib to a patient with early-stage endometrial carcinoma for whom you are recommending adjuvant chemotherapy based on improved outcomes seen in RUBY/DUO-E/NRG-GY018?

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...

In a patient with HER2+ advanced endometrial cancer, do you include IO(+/- olaparib) in their treatment regimen, or only trastuzumab in addition to carboplatin/paclitaxel?

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

Would you recommend adjuvant chemo+IO +/- olaparib for patients with occult stage III disease identified after staging surgery with no measurable residual disease?

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...

4 Answers available

For patients with advanced endometrial cancer, are the improved outcomes in PFS from DUO-E/RUBY/NRG-GY018 sufficient to move immunotherapy to the frontline for all presuming FDA approval?

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 ...

For patients with locally advanced rectal cancer who desire organ preservation and can tolerate fluoropyrimidine but not oxaliplatin, what is the appropriate treatment approach?

Following the BRUIN data in mantle cell lymphoma, will you routinely treat with pirtobrutinib following a covalent BTKi?

Is the data sufficient to change your practice?

Will you recommend pirtobrutinib following a prior covalent BTKi in patients with cardiac comorbidities?

Does cumulative exposure to BTKi increase potential risk of cardiac toxicity?

What subsequent therapies did patients receive after progressing on pirtobrutinib in the mantle cell BRUIN trial population?

Should pirtobrutinib be viewed as a bridge to CAR-T or transplant or a destination therapy?

Are there biomarkers or other factors to help predict which patients with MCL are most likely to benefit, or not, from pirtobrutinib following a prior covalent BTKi?

How do you predict which patients may be in a high risk group and less likely to benefit from a second BTKi?

What are the factors that convince you to not immediately treat mantle cell lymphoma and to follow a course of "active surveillance"?

Is there a specific Ki67 percentage? P53-negativity?

What is the recommended follow-up/surveillance schedule following organ preservation treatment approach for cT1-2N0 rectal cancer?

Taking into account follow up from NEO, OPERA and other organ preservation trials?

Is there a correlation between rectal cancer stage and dose response to radiotherapy?

Dose-escalation RT trials have had mixed results in the past for advanced rectal cancer, while in the early rectal stage there is a tendency towards a...

For patients with cT1-T3 cN0 cM0 mid/low rectal cancer seeking organ preservation, what treatment approach do you recommend?

How do you weigh definitive chemoRT vs minimally invasive surgical approach with neoadjuvant chemo followed by transanal excision, in light of results...

How does the potential for a patient to accept or forego adjuvant tamoxifen factor into your recommendations on adjuvant RT for DCIS?

Are there specific patient populations in which you may feel comfortable with a patient selecting only one adjuvant therapy approach (tamoxifen vs RT)...

How do you sequence radiation and capecitabine in breast cancer patients receiving adjuvant capecitabine for residual disease after neoadjuvant chemotherapy?

It is not clear from CREATE-X whether radiation was before or after capecitabine. Is there a preferred approach?

6 Answers available

What is the role of liquid biopsy in patients with metastatic castration resistant prostate cancer to asses BRCA1/2 or other mutations and consider PARP inhibitors?

Alternatively, is a biopsy of a metastatic bone lesion preferred in a patient who has already progressed on chemo and hormonal therapy and has bone-on...

Are there any unique toxicity concerns with combination of ramucirumab/pembrolizumab as compared with other available treatments for metastatic NSCLC?

How do you counsel patients on the available second line options?

Are there differences in efficacy of ramucirumab + pembrolizumab based on extent and duration of response to first line chemo/pembro?

Did S1800a stratify by prior treatment response? Would you choose different 2L treatment for a patient who progresses rapidlly on pembro + platinum do...

What do you view as the role for docetaxel+ramucirumab for patients with metastatic NSCLC in light of LUNG-MAP S1800a data?

Would you still use ram/doce in 3rd or later lines after ram/pembro?

Are CHEK2 mutations a contraindication for breast conservation therapy with lumpectomy + RT?

Should patients with moderate penetrance pathogenic variants be managed similar to BRCA patients and consider risk reducing contralateral mastectomy?&...

4 Answers available

When, if ever, would you recommend risk reducing BSO in patients with moderate penetrance breast cancer germline mutations?

Genes such as ATM, CHEK2, PALB2, RAD51C/D, BRIP1 seem to show some potential increased risk of ovarian cancer. Should these patients under prophylacti...

Would you consider use of PARP inhibitors in patients with metastatic breast cancer with moderate penetrance germline mutations such as CHEK2, ATM, RAD51?

What about a higher penetrance PV such as PALB2? See JCO OGR 8/2021 by @Mark E. Robson discussing management of non-BRCA pathogenic va...

For which non-BRCA pathogenic germline variants, if any, might you consider recommending chemoprevention with SERM/AI?

In a scenario where patient's other clinical/familial risk does not sufficiently qualify them? See JCO OGR 8/2021 by @Mark E. Robson discussing manag...

How do you counsel patients on the efficacy of breast cancer risk reduction strategies such as breast MRI surveillance or bilateral mastectomy for those considered high risk by polygenic risk score, pathogenic variants, and/or family history?

Specifically do we know by how much each intervention reduces the risk of developing MBC or increase breast cancer specific as well as overall surviva...

What is your strategy for ovarian suppression if unable to achieve goal estradiol levels with leuprolide 3.75mg monthly dose?

Data from the SOFT/TEXT trials showed clinical benefit in ovarian suppression + aromatase inhibition for high risk, premenopausal ...

Is there any role for bisphosphonate or alternative bone-modifying agents use in SMM in the absence of other indications for its use?

Is there any role for early stem cell mobilization and collection during the SMM phase?

Do you worry about the ability to collect stem cells (at the time of progression to MM) if someone with SMM has been on prolonged lenalidomide?

How long do you treat with IMID in a case of smoldering multiple myeloma?

Does high risk cytogenetics as a sole abnormality influence your treatment decision for smoldering multiple myeloma?

How do you decide on the duration of endocrine therapy for premenopausal women who receive chemotherapy and AI/ovarian suppression according to TEXT/SOFT?

Do you recommend ovarian suppression in all premenopausal women under age 35 with ER positive breast cancer based on the SOFT/TEXT data, regardless of other risk features?

For example, is this still your approach in women with small tumors or node negative disease?

Before re-challenging a patient with ICI after grade 1-2 pneumonitis, do you re-image to confirm resolution of pneumonitis?

Is there a period of time after which you would not resume ICI after a patient has had an irAE and required a prolonged steroid taper?

Would the need for infliximab/MTX/nonsteroidals to control initial irAE affect your decision to rechallenge these patients with ICI?

Do you recommend frontline bevacizumab with carbo/taxol in patients with advanced epithelial ovarian and BRCA mutation who will be receiving olaparib maintenance?

In light of GOG-252, are there any situations where IP chemotherapy would be preferable following debulking of advanced epithelial ovarian cancer?

When do you choose dose-dense chemotherapy v. q3 week therapy in advanced epithelial ovarian cancer?

How do you choose 1st line therapy for recurrent cervical cancer?

Would you be more or less likely to use a cisplatin-containing regimen if a patient had previously responded to chemoradiation with concurrent cisplat...

How do you determine which systemic therapy to recommend in the 2nd line setting for metastatic, PD-L1 NEGATIVE cervical cancer?

Is pembrolizumab considered standard of care in the 2nd line treatment of recurrent cervical cancer?

Does the phase II KN-158 provide sufficient evidence to change management?

Would you recommend 1st line pembrolizumab for PD-L1 positive recurrent/metastatic cervical cancer patient who is not a candidate for or refuses chemotherapy?

When do you recommend PD-L1 testing for patients with recurrent cervical cancer?

Should this be done at the time of recurrence or after failure of 1st line therapy for recurrence?

For women who have had either embryo or oocyte cryopreservation, do you also recommend administering GnRH analogs?

Is there a subset of breast cancer patients who may benefit more from GnRH analogs for fertility preservation compared to others?

How do you approach and counsel women with high risk, early stage breast cancer requiring chemotherapy for whom fertility preservation is a major concern?

Is there any data on the use of PARP inhibitors in patients with metastatic urothelial carcinoma with deleterious DDR mutations?

Is there a role for DDR gene mutation or tumor mutation burden/load in predicting response to immunotherapy in urothelial cancer?

How do you choose among the available PD-1/PDL-1 inhibitors approved for metastatic bladder cancer?

There are now five PD-1/PDL-1 inhibitors approved for metastatic bladder CA, one (Atezolizumab) as first-line therapy in cisplatin-ineligible patients...

Would you hold immunotherapy if a patient with metastatic melanoma has stable disease for 6 months?

If so, after what duration?

Would you consider stopping nivo/ipi combination after a CR in a patient with metastatic melanoma?

Can you extrapolate the data on Durable Complete Response After Discontinuation of Pembrolizumab in Patients With Metastatic Melanoma to patients on a...

Is there a difference in the durability of CR based on the dosage of pembrolizumab used in metastatic melanoma?

In this study, doses of 2mg/kg Q3wks, 10mg/kg Q3wks and 10mg/kg Q2wks were used. What did the majority of these patients in CR receive?

How do you present the trade off between a small chance of a sustained response for a new drug at the expense of potential worsening quality of life?

Has precision medicine changed how you consent patients for treatment?

When discussing immunotherapy with patients, how do you frame the conversation in a way that acknowledges the fact that many patients do not respond but allows for hope for a durable response?

Is there a role in sending liquid biopsy for patients progressing on ALK inhibitors?

In patients with T790M mutation and progression of disease on osimertinib, is there any utility in checking peripheral blood cDNA for continued presence or absence of the T790M mutation?

How are you using liquid biopsy in the routine management of your patients with metastatic NSCLC?

Are you using ctDNA blood tests for targetable mutations at the time of diagnosis, at the time of disease progression, or not at all?

Can ctDNA be used to evaluate response to checkpoint inhibitors in NSCLC when pseudoprogression is suspected on CT imaging?

Do you consider MSI testing for mCRPC?

Based on 2-3% MSH2 mutation and 1% MLH1 mutation rates in metastatic disease regardless of castration sensitivity, should we be looking for this earli...