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The best example of how well people can potentially tolerate [pembrolizumab] would be former President Jimmy Carter. He's 91 years old, he's getting this therapy, and he's continuing to build houses and travel. Certainly these are easily tolerated therapies." DALE SHEPARD, MD, PHD, MEDICAL ONCOLOGIST, CLEVELAND CLINIC had their a nswer as to how the tumors skir ted the immune system; now it was a matter of f inding the right medication to interrupt that process. FAST-TRACKED SOLUTION In 2014, Dr. R ibas was lead resea rcher on the Phase 1 tria l of pembrolizumab, a med icat ion t hat helps d i sr upt t he response to misleading sig na ls sent by mela noma cells a nd restore the body 's abilit y to detect a nd ta rget the ca ncer. T r i a l p a r t i c i p a n t s r e c e i v e d a n i n f u s i o n o f t h e i m m u n o t h e r a p y med icat ion once ever y t wo to t h ree week s t h rou g hout t he cou rse of t he t r i a l . It qu ic k ly b e c a me c le a r t h a t t he medication wa s successf u l. The avera ge response rate for a ll patients w a s a p p r o x i m a t e l y 3 7. 5 p e r c e n t . Enrollment spiked and pembrolizumab was g iven a brea kthrough desig nation b y t h e F DA , a l lo w i n g r e s e a r c h er s to license the medication a nd receive F D A a p p r o v a l b e f o r e c o m p l e t i n g fur ther tria ls in order to g ive patients immediate access to this potentia l ly lifesaving treatment. " What this class of medication does is it blocks the [PD-1] receptor so tumors ca n secrete a l l the PD -L1 a nd PD -L2 that they wa nt , but it won't suppress t he T cel ls," says Da le Shepa rd, M D, PhD, medica l oncologist with Cleveland Clinic, who reg u la rly treats patients w it h pembrolizumab. " This rea l ly is kind of a brea kthrough — a novel way to treat cancers. Now, the immune system recognizes this tumor as being foreign, a nd it ca n mount a response." ONE DRUG, MANY CONSIDERATIONS Phase 2 a nd Phase 3 testing of pembro- liz umab conti nued to show prom ise i n ha lti n g t u mor prog ression over a longer span of time when patients whose m e l a nom a h a d b e en u n r e s p on s ive to ot her t herapies were moved onto t he ne w pr ot o c ol . Ph a s e 2 s howe d a 2 5 p er c ent r e s p on s e r a t e a mon g patients who had ex hausted a ll other treatments. In Phase 3, the six-month prog re s sion-f re e s u r v iv a l r at e w a s 46 percent for those on pembrolizumab, compa red w ith 26 percent si x-month progression-free sur viva l rates a mong t hose who u sed a not her mel a nom a treatment, ipilimumab. Since its initial approval for melanoma, pembrolizumab has also been approved to help treat other cancers, including metastatic non-small cell lung cancer, and is being investigated for cancers of the bladder and other locations. Pembrol i z u m a b's side ef fec t s a re typica lly limited to rash and inf luenza- li ke ma la ise, according to Dr. R iba s, and are significantly different from and milder than those of chemotherapy and other mela noma treatments. T hou g h it ha s proved ef fec t ive i n specif ic settings a nd patients, contin- ued resea rch is necessa r y to ensure appropriate patients a re ta rgeted with this medication, Dr. Shepa rd cautions. Im mu not herapy cost s i nt o t he t en s of t housa nds of dol la rs per ca se, a n additiona l consideration for patient ta rgeting a nd for its use as a combina- tion therapy. " E v e n t h o u g h t h e s e a r e a m o r e genera l way to treat [ca ncers], they 're probably goi ng to have to be used i n combination with something else, in a multipronged approach," Dr. Shepa rd says. " We have a lot of tria ls coming a round now looking at immunotherapy plus chemotherapy or a targeted therapy or a nother immunotherapy." Mel a nom a resea rch cont i nues t o move for wa rd. New a nti-vira l medica- tions a re show i n g prom ise a nd may e v e n le a d t o a m e l a n om a v a c c i n e , a nd cont i nued work i s u nder way t o understa nd which patients a re best to ta rget w it h i m munot herapy such a s pembrolizumab and how the medication works in conjunction with others. T h at 's re sea rch D r. R iba s i s s t i l l involved in a s he tr ies to per fect t he application of his tea m's work. " We'll continue lea rning more, a nd we'l l sta r t understa nding if patients respond long-term or why not," he says. " We'll start to understand what 's miss- ing there a nd how we ca n cha nge it." ■ M D N E W S . C O M /// M D N E W S L O N G I S L A N D ■ 2 016 2 5