Practice changing trials
1. ARASENS
2. PROPEL
3. MAGNITUDE
References:
1. ARASENS: https://www.nejm.org/doi/full/10.1056/NEJMoa2119115
2. PROPEL: https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.6_suppl.011
3. MAGNITUDE: https://ascopubs.org/doi/abs/10.1200/JCO.2022.40.6_suppl.012
Metastatic castrate resistant prostate cancer mCRPC
metastatic castration sensitive prostate cancer mCSPC
Biochemical progression M0
High risk prostate cancer- adjuvant treatment
MONARCH 2- Abema with fulvestrant in pre, peri and post menopausal women showed OS benefit ( front line, after progression on adjuvant AI).
MONALEESA trials- Ribociclib OS benefit in the above groups.
Ribociclib:
Dose 600 mg daily 3 weeks on, 1week off ( 28 day cycle)
Baseline:
1. Electrolytes and EKG at baseline, C1D14 and C2 D1. Then electrolytes day 1 of first 6 cycles. EKG periodically and as clinically indicated. QTc prolonged 4%. Check CBC q 2weeks for first 2 cycles, then at the beginning of each cycle.
2. Monitor of symptoms of hepatotoxicity 14%
3. Monitor for ILD symptoms ( 0.6%).
4. Check med list for any drugs that may interact or prolong Qtc
5. Cannot use Ribo with tamoxifen due to QTc prolongation.
Ref: NCCN
If RS>26 --> chemo in all comers
Premenopausal women
1. If node neg and RS < 15--> no chemo per TAILOR X
2. If node neg and RS 16-25--> some chemo benefit but possibly due to OFS in women less than 50 yr
3. If node positive and RS < 26--> some chemo benefit per PONDERRX
Post menopausal women
If RS< 26, even with 1-3 LN, ok to omit chemo.
Initial assessment:
1. Is there associated fever or uncontrolled pain? ( grade 4)
If answer is yes to grade 4--> arrange admission--> draw baseline labs, CBC, blood /urine culture, CMP, start broad spectrum antibiotics covering staph and strep. Fluids, antiviral, antifungal etc Wound care.
If NO, assess if grade 3
2. Is the rash covering more than 30% of BSA, causing pain and limitation of self care ADL? ( grade 3): hold cancer treatment, treat pain, bleeding, any wounds. Check labs and vitals. Blood tests and cultures. Topical and systemic agents.
3. If grade 1 or 2, assess percentage: < 10% or 10-30%
maculopapular, pustular, acneiform
hyperkeratosis, moisture, erythema, tenderness, swelling, loss of sensation, open wounds
Drugs
Tyrosine Kinase Inhibitors (e.g.Gefitinib, Erlotinib, Afatanib and Lapatinib)
mTOR Inhibitors (eg. Everolimus)
Dabrafenib
Cetuximab, panitumumab
1. NPM1 and FLT3 mutations in patients with AML on Aza "maintenance" or ongoing treatment for those unable to proceed to transplant after achieving CR still produces response.
2. What is the difference between Sweet's syndrome, leukemia cutis and myelodysplasia cutis?
Sweets: inflammatory dermal infiltrates of neutrophils. Majority cells non clonal but 20% clonal.
Histiocytoid Sweet's.: immature myeloid non blasts. Subset clonal.
Leukemia cutis: infiltrates of blasts in skin. All clonal and related to underlying bone marrow or blood malignancy.
Myelodysplasia cutis: infiltrates of immature neutrophils but not blasts. Clonally related. ( midway between Histiocytoid Sweet's and Leukemia cutis)
3. Abatacept is particularly helpful in cGVHD with bronchiolitis obliterans.
4. Clonal hematopoiesis of indeterminate potential (CHIP) is the presence of a clonally expanded hematopoietic stem cell caused by a leukemogenic mutation in individuals without evidence of hematologic malignancy, dysplasia, or cytopenia. CHIP is associated with a 0.5-1.0% risk per year of leukemia. CHIP is also sometimes known as age-related clonal hematopoiesis (ARCH). Cases of cytopenia and clonal hematopoiesis are described as clonal cytopenias of undetermined significance (CCUS). CHIP clonal hematopoiesis and idiopathic cytopenias of undetermined significance (ICUS) have some degree of overlap . The most common mutation is on the DNMT3A gene, followed by TET2 and ASXL1. CHIP requires absence of cytopenia, evidence of clonal neoplasm and absence of evidence of monoclonal B cell lymphocytosis, PNH and MGUS. It is a benign condition. However, monitor for cardiac disease since these people have a higher risk of MI.
ICUS versus CCUS: ICUS does not have clonality or mutant genes typically. CCUS has both.
To describe patients in whom MDS is possible but not proven, the term of idiopathic cytopenia of undetermined significance (ICUS) has been introduced. To be classified in this provisional category, patients must have relevant cytopenia in one or more lineage (hemoglobin <11 g/dL, neutrophil count <1.5 × 109/L, platelet count <100 × 109/L) that is persistent for at least 6 months, cannot be explained by any other disease and does not meet diagnostic criteria of MDS. Reference ASH.
5. CMML- one subtype of CMML does better than others – these patients have a TET2 mutant/ASXL1 wild-type genotype. They not only have better survival rates, but also have more durable responses to HMAs. Reference ASH.
Who, what , where, when, how?
Who: Patient factors
What: disease factors
Where extent of disease:
When: timing of treatment
How: details of treatment, monitoring, short term and long term side effects, surveillance
