Info
Triple negative disease
- Initial work-up: PD-L1 IHC, NGS, germline genetic testing
- Targeted/ IO:
- If PD-L1 > = 1%: Atezo + nab-paclitaxel (IMpassion130, NEJM 2018;379:2108)
- If CPS > = 10, pembro + chemo (nab-paclitaxel, paclitaxel, gem + carbo) (KEYNOTE-355 Lancet 2020;396;1817). PFS benefit for both
- If BRCA1/2 germline positive, consider
- olaparib
- talazoparib
- ↑ PFS (OlympiAD, NEJM 380;985; EMBARCA, NEJM 2018;379:753)-note: ORR & PFS benefit for olaparib seen in somatic BRCA1/2, germline PALB2 as well in phase II setting (TBCRC 048, JCO 2020;36:4274)
- For 3rd line: Sacituzumab-govitecan (ADC to Trop2)-demonstrated ↑ PFS & ↑ OS benefit (ASCENT, NEJM 2021;384;1529)
- Monitor for pancytopenia
- NTRK fusion → laro/entrectinib
Chemo
Sequential single-agent chemo preferred over combination, but combo could be considered if significant burden of dz & rapid progression (no OS benefit of combo AT vs. A −>T but ↑ RR w/ combo) Combo docetaxel/cape ↑ OS vs. doce alone (JCO 2002;20:2812) & paclitaxel/gem ↑ OS vs. paclitaxel alone but incl. tox & never tested vs. sequential Rx (JCO 2008;26:3950) No standard sequence of agents, although weekly paclitaxel is typically 1st-line (CALGB 40502) → cape & eribulin 2nd/3rd Taxanes: Paclitaxel, docetaxel, & albumin-bound paclitaxel; paclitaxel weekly > q3wks (↑ OS) (JCO 2008;26:1642) & paclitaxel = albumin-bound paclitaxel but cheaper Other antimicrotubule agents: Eribulin & vinorelbine; eribulin > “Physician’s choice” (↑ OS) for 3rd-line & beyond (EMBRACE, Lancet 2011;277:914) Anthracyclines: Doxorubicin, epirubicin, & pegylated liposomal doxorubicin; consider addition of dexrazoxane if >300 mg/m2 of lifetime doxorubicin exposure (JCO 1999;17:3333); pegylated liposomal doxorubicin is less cardiotoxic Antimetabolite: Cape & gemcitabine Less commonly used: Infusional 5-FU, ixabepilone, vinblastine, etoposide, cis, cyclophosphamide, mitoxantrone, irinotecan Combinations: Gem/carbo, CAF, FEC, AC, EC, AT, CMF, doce/cape, gem/taxol, cape/ixabepilone