Paolo Tarantino, Research Fellow Dana-Farber Cancer Institute and Harvard Medical Schoolpost, shared on LinkedIn:
“Ten reasons why I would favor the newly FDA-approved gedatolisib doublet (fulvestrant/gedatolisib) over the triplet with palbociclib:
- VIKTORIA-1 was not designed to compare the two geda arms – yet, the PFS improvement over fulvestrant was similar with or without palbo (HR 0.24, HR 0.33, with overlapping 95%CI)
- ORR was also similar, 31% vs 28%, consistent with the idea that palbo does not add much activity
- there is no OS advantage from adding palbo, and the current favorable OS trend is similar in both geda arms (HR 0.69 and 0.74)
- the PIK3CAmut sub-study of VIKTORIA-1 also confirmed this pattern, with no apparent benefit from the addition of palbo to the doublet
- using palbo after prior CDK4/6i has failed to improve outcomes in two randomized trials (PACE, PALMIRA)
- the triplet clearly adds toxicity. >50% grade 3 neutropenia (0% without palbo) and higher rates of severe stomatitis and nausea
- treatment-related deaths only occurred with the triplet, with two grade 5 toxicities (vs none with the doublet)
- the triplet adds logistic burden. A nearly weekly IV infusion and a monthly shot are already burdensome. Adding a third anticancer drug with distinct route of administration and frequent requirement for dose holds further adds complexity.
- the triplet further adds costs
- we treat this disease to achieve disease control with preservation/improvement of QoL. Adding a third drug which adds toxicity and may worsen QoL, without clear long-term benefit, does not sound like a good deal.”
