54 year old female with ER/PR pos, HER2 neg metastatic breast cancer with extensive bone metastasis, started on 1L therapy with palbociclib + exemestane in 2022, now with progression of osseous metastasis. Guardant 360 liquid bx showed ESR1 and RB1 mutation. Plan to switch to Elacestrant. Question is - is there any role for continuing the Palbociclib? Does RB1 confer resistance to CDK 4/6i and hence, she may have acquired resistance to both the endocrine therapy and CDK 4/6i? If she didnt have any other co-existing RB1 mutation, should the CDK 4/6i be discontinued?
Good question. I would not continue the palbociclib past progression, based on the PACE trial which showed that it was not beneficial to do this (SABCS 2022). But I do think you could switch to ribociclib, based on the MAINTAIN trial which showed benefit from that change. I don't know of any evidence that either ESR1 or RB1 confers resistance - and in fact, there is some evidence against this (PMID 37141549). So would go ahead with elacestrant and would be inclined to add ribociclib if insurance will cover.
