As target therapy continue to advance, increasingly first line treatment will be a combination of these therapy
and cost will be increasingly the limiting factor:
After Paloma, is it right to propose Letrozole alone (Vs a combination with Palbociclib) particularly in Metastatic disease.  One may want to try Letrole alone and add Palbociclib when there is progression but do remember the study compare the combination to Letrozole alone upfront with a doubling of the progression free survival...Then come other aspects of the problem, What is the role of Fulvestrant or should we keep it after the failure of the combination...and then one will ask should you stop CDK4 inhibition while using Fulvestrant?  At least it is a good thing to have these choices for our patients!
It is important to mention that combination do not always work better:

Clemons:" Result suggest that the addition of vandetanib to fulvestrant did not improve biomarker response, PFS or OS in patients with bone metastases. Baseline bone turnover was prognostic for PFS and OS."  I should stress that Vandetanib is an anti-VEGF (different apple all together!)

When Her-2 is positive
Boix-Perales et al:
"The demonstration of clinical benefit for pertuzumab was based on a single, phase III, randomized, double-blind, placebo-controlled trial comparing the efficacy and safety of pertuzumab plus trastuzumab plus docetaxel versus placebo plus trastuzumab plus docetaxel in previously untreated patients with locally advanced or metastatic HER2-positive breast cancer."
Here 18 months VS 12  PFS
and 80 V 69  OS

Now is it right in Metastatic Melanoma to give an Anti-BRAF knowing well it is a short lived (or add Ipilimimumab after 3 to 4 months? or of course a combination Ipilimumab-Nivolumab...what is the cost?  Is it worthwhile an English may ask?  But here comes the choices again...Target therapy, still creeping up in all of us...But clearly the way to go...