Drug tar­gets can­cer mu­ta­tion rather than area of growth

The Denver Post - - NATION & WORLD - By Lauran Neergaard

WASH­ING­TON» Colon can­cer. Uter­ine can­cer. Pan­cre­atic can­cer. What­ever the tu­mor, the more gene mu­ta­tions lurk­ing in­side, the bet­ter chance your im­mune sys­tem has to fight back.

That’s the premise be­hind the re­cent ap­proval of a land­mark drug, the first can­cer ther­apy ever cleared based on a tu­mor’s ge­net­ics in­stead of the body part it struck first. Now thou­sands of pa­tients with wors­en­ing can­cer de­spite stan­dard treat­ment can try this im­munother­apy — as long as ge­netic test­ing of the tu­mor shows they’re a can­di­date.

“It’s like hav­ing a lot­tery ticket,” said Johns Hopkins on­col­o­gist Dr. Dung Le, who helped prove the new use for the im­munother­apy Keytruda. “We’ve got to fig­ure out how to find these pa­tients, be­cause it’s such a great op­por­tu­nity for them.”

To­day, doc­tors di­ag­nose tu­mors by where they orig­i­nate and use ther­a­pies specif­i­cally tested for that or­gan. In con­trast, the Food and Drug Ad­min­is­tra­tion la­beled Keytruda the first “tis­sue-ag­nos­tic” treat­ment, for adults and chil­dren.

The rea­son: Seem­ingly un­re­lated can­cers oc­ca­sion­ally carry a com­mon ge­netic flaw called a mis­match re­pair de­fect. De­spite small stud­ies, the FDA found the ev­i­dence con­vinc­ing that for a sub­set of pa­tients, that flaw can make solid tu­mors sus­cep­ti­ble to im­munother­apy doc­tors oth­er­wise wouldn’t have tried.

“We thought these would be the hard­est tu­mors to treat. But it’s like an Achilles heel,” said Hopkins can­cer ge­neti­cist Bert Vo­gel­stein.

And last month FDA Com­mis­sioner Scott Got­tlieb told a Sen­ate sub­com­mit­tee his agency will sim­plify drug de­vel­op­ment for dis­eases that “all have a sim­i­lar ge­netic fin­ger­print even if they have a slightly dif­fer­ent clin­i­cal ex­pres­sion.”

It’s too early to know if what’s be­ing dubbed pre­ci­sion im­munother­apy will have last­ing ben­e­fits, but Hopkins es­ti­mates about 4 per­cent of can­cers are mis­match re­pair-de­fi­cient, po­ten­tially adding up to 60,000 pa­tients a year. Widely avail­able tests that cost $300 to $600 can tell who’s el­i­gi­ble.

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