Breast cancer updates 2022

 1. KN 522 Early TNBC : 8% EFS benefit and 8% Distant met free survival benefit over 3 yr. OS data are not statistically significant at 3 yr with the addition of Keytruda to carbo taxol- AC. My personal comment on this is that I would not use the 3 week AC dose as in this trial just to accommodate keytruda regimen. We know that DDAC is better in high-risk patients. Unanswered questions include: whether should Keytruda be continued if path CR is achieved. What if path CR is not achieved in BRCA + patients? PARP or Capecitabine +/- keytruda?

2. Monarch- E High risk node positive ER+- Ki 67 prognostic but not predictive of abema benefit. Inclusion criteria N2 disease. If N1 disease, had to have either T3, G3, or ki67 20% or higher disease. absolute improvements in 3-year IDFS and distant relapse-free survival rates of 5.4% and 4.2%, respectively, for the ITT population

3. Brightness trial TNBC: This was an interesting trial presented at ESMO 2021. The key questions were to determine if adding carboplatin and/or veliparib to standard AC-T improved outcomes. Veliparib made no difference even in BRCA germline mutated patients. Carboplatin improved EFS and path CR in all comers.

4. Olympia BRCA 1/2 : 1 yr adjuvant olaparib for high risk HER 2 neg patients BRCA 1/2.

TNBC 80% or ER+ 18%. 50 % received neoadjuvant. 7% DDFS benefit in 3 yr.  9% IDFS benefit.

OS data 3 yr OS improvement 3.8%

CPS EG 3 or higher indicates high risk of relapse in ER+ patients.

Calculator:

http://www3.mdanderson.org/app/medcalc/index.cfm?pagename=bcnt

5. Rx PONDER

Recurrence score 0-25 Post menopausal women with 1-3 LN, no chemo benefit

Premenopausal women: 5% benefit in IDFS and 2.5 % benefit in distant recurrence free survival.

Benefit was seen in pre-menopausal women with micro mets and macro mets.

6. TEXT and SOFT trials:

OFS: 13 yr follow up 3.3% OS benefit with exemestane with OFS compared to tamoxifen with OFS

Non small cell lung cancer ASCO 2022 update

 

1. Stage IB through IIIA --> if resectable--> surgery then 4 cycles adjuvant chemo.

If margins positive--> repeat resection ( preferred) or RT

Recent updates:

Add adjuvant atezo for 1 yr after 4 cycles adjuvant chemo if PDL1= or>1% for a DFS benefit

If EGFR mutant, add osimertinib for 3 yr after 4 cycles chemo

OR if able to use neoadjuvant chemo io do 3 cycles nivo with carbo taxol--> surgery---> 6 months nivo--> OS benefit.

My take on this:

Early stage resectable, do NGS to identify EGFR/ALK mutations. If positive, plan for surgery, adjuvant chemo, and then osimertinib for 3 years. This may change once the results of the NeoADAURA trial  become available. ADAURA showed a  DFS benefit with 90% patients with no disease progression at 5 yr and median DFS of 5.5 yr.

If no driver mutations, and resectable do neoadjuvant nivo with carbo taxol. High rate of path CR 37% and OS benefit.

ALK mutations: ongoing trials using alectinib

2. A side note on KRAS mutated versus wild type patients: best rx available now is chemo IO even if PDL1 > 50% do not use single agent IO.

3. Seribantumab trials in those with NRG1 mutations ( rare mutations) is a HER 3 antibody ( similar to Perjeta) and has a 33% response in this population comparable to chemo. Diarrhea.

TDxd in exon 19 or 20 insertions - ongoing trials

3. IIIB/IIIC unresectable

concurrent chemo RT followed by 1 yr durva in all comers irrespective of EGFR mutation status. Although in Europe, these patients are not given durva. Ideally enroll in a clinical trial after concurrent chemo RT.

NRG Lung 004 trial: in patients with PDL1> 50% omit chemo and use concurrent IO RT followed by maintenance IO ( durva). Bottom line, this was safe. Efficacy data pending.

VEXAS syndrome

 

What is VEXAS syndrome: A syndrome with a mix of inflammation and hematologic disorder.

Often associated with MDS Or MGUS.

UBA1 gene inactivating mutations

Most effective rx so far to date: Jakafi ( Blood Aug 2022)

Adult-onset syndrome that links seemingly disparate hematologic and autoimmune symptoms. The first description of the disorder, called VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome, was published in The New England Journal of Medicine (NEJM) in December 2020

https://www.nejm.org/doi/full/10.1056/NEJMoa2026834

https://ashpublications.org/ashclinicalnews/news/5960/The-Vexing-VEXAS-Syndrome?searchresult=1

COVID and VTE prophylaxis

 1. Non critically ill hospitalized patients: use rx dose heparin

2. Critically ill hospitalized patients: use trophy dose heparin

Avoid rivaroxaban

Except for NICE guidelines, which recommend 7 days post-discharge prophylaxis

Blood Aug 2022

Smoldering myeloma

Smoldering myeloma work up

Blood Aug 2022

Baseline tests:

CBC, B12, folate, iron studies

Creatinine, calcium, ALKP

UPEP, SPEP, IFE, FLC

NT-pro BNP

PET CT or whole body low dose CT or MRI spine and pelvis

Repeat in 3-6 months: creatinine, Calcium, CBC, SPEP IFE, FLC

Anemia labs if Hb drops

24 hr urinary protein, NT BNP every 12 months

Imaging and bmbx when progression suspected