58 y.o healthy female. rectal cancer w/ large liver and lung mets. pMMR, Her-2. Muncinous. NRAS mutated. Tempus has no suggestions. In 2023 started FOLFOX+bev, progression by 4 to 5 months later. Changed to FOLFIRI+bev. Stable disease 2023. Continued. Later in 2023, slightly worse (in the 3-5 mm range at most sites of disease.) In hindsight, perhaps I could've done FOLFIRINOX, but she's seen both agents now, and really hasn't had a meaningful response. Now starting Lonsurf+bev. I don't have an NRAS mutation trial near me, but I don't know how helpful that would be anyway. Other suggestions for effective tx? PS is still 0. no pain from lesions at start or now, which are rather large. Again, mucinous.
I am assuming you meant to write negative after HER2. NRAS mutation studies are hard to find. there are more for KRAS mutant CRC, and so probably it would be a basket study for KRAS/NRAS and would require travel, as you said. In terms of standard-of-care chemo, i don't know that FOLFIRINOX would have made a difference. I don't typically use it in the 2L either. Unfortunately, this sounds like a pretty resistant tumor based on the rate of progression through standard therapies. Since there is liver involvement, most of the chemo/immunotherapy combinations (either off label or in a trial) are unlikely to work. I agree with Lonsurf+bev. I would probably do fruquintinib next, but I do not anticipate good responses. i have had a few surprises with these refractory agents being somewhat effective, but it is usually in patients who have less aggressive disease than you described. If it has been several months since the last exposure, sometimes i will recycle FOLFOX or FOLFIRI to see if you can get a response. If a high liver burden, i would consider Y-90 to the liver to try and stabilize those tumors.
