METASTATIC MELANOMA

1.IPILIMUMAB ( ANTI-CTLA-4), BETTER THAN DTIC
Dose in front line is 10mg/kg every 12 weeks but the FDA approved at 3mg/kg every 3 weeks 4 times
*Ipilimumab is one of the most significant developments here since its curb leads to a plateau state of survival which begins to show at approximately 2 years,
at 1 year, survival in metastatic disease is at 44-46%
at 2 years, it is at 22% (with 3Y survival at 20.8% in STUDY 024)
there after it does not drop off as much, suggesting there are few cures
*This is reminding us the curb of IL-2 in which few cures are observed.
*Ipilimumab is not for those with rapidly progressive disease, activity is delayed.
*Active even in Brain Mets

*10mg/kg did better than 3mg/kg but at greater Toxicity.
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2. * IL-2 the "old dog" is still going strong, tough on patients and only given in specialized centers,
still kicking as an option because of the cures it gives
 * Given only to selected patients with skin and lung disease, stress test needed if over 50, and smokers,
after abdominal surgery, wait for 8 weeks before initiating treatment.
*Median duration of response 6.5 months
*17% Response Rate (6% CR) and (11% PR)
69% of those with CR will be cured, and 47% of PR will stay stable (a cure of sort)
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3.VEMURAFENIB for those expressing BRAF-V600  (ON all the times)
90% suppression of pERK needed for clinical activity
* after Vemurafemib, patients respond poorly to Ipilimumab
* gives the longest Progression free survival 15.9 months
*No survival tail here, the lesions quickly melt, but when they come back, death subsequently ensues.
*in one series,patients 20-30 Years of age are 100% BRAF positive
*Combination Ipilimumab and Vemurafenib proved to be too toxic for the Host/patient
*Vemurafenib combination with Anti-MEK could eventually replace the single agent.
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4. ABRAXANE has replaced DTIC as Chemotherapy to go to first,
other Option Taxol-Carbo in desperate states such as recurrence after failure of Vemurafenib
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5. New kid on the block, PD-L1, provides a new option for recurrence after Vemurafenib or BRAF
WT mutated patients, "ANTI-DEATH"

Attended Mark G Kris lecture on Lung Cancer  (KRIS IS FROM MSKCC)

Now genetic sequencing is important

Prescribe the following

1)  EGFR-------------ERLOTINIB, GEFITINIB
2)  ALK-----------------CRIZOTINIB
3) HER-2--------------HERCEPTIN, LAPATINIB
4) BRAF -------------------VEMURAFENIB
5) ROS-1-----------------CRIZOTINIB  (AGAIN)
6) RET--------------------------VANDETANIB  (CABOZANTINIB)
7)MET------------------------CRIZOTINIB (AGAIN)

NICE THE PRESCRIPTION SPELLING OUT ONLY THE GENE SEQUENCING, AND LET YOUR PHARMACIST DO THE REST.
QUESTION: COULD THESE DRIVER GENE ABNORMALITIES BE THE SAME IN TRIPLE NEGATIVE BREAST CANCER?