Mer­ck­'s Keytru­da makes the cut as a sec­ond-line monother­a­py for cer­tain esophageal can­cer pa­tients

Mer­ck’s cor­ner­stone check­point in­hibitor Keytru­da has added an­oth­er jew­el to its crown.

The US drug­mak­er on Wednes­day dis­closed that the PD-1 drug had won ap­proval as a monother­a­py for pa­tients with re­cur­rent lo­cal­ly ad­vanced or metasta­t­ic squa­mous cell car­ci­no­ma of the esoph­a­gus, whose tu­mors ex­press PD-L1, and whose dis­ease has pro­gressed de­spite one or more pri­or lines of sys­temic ther­a­py.

About 17,650 new esophageal can­cer cas­es will be di­ag­nosed this year in the Unit­ed States, the Amer­i­can Can­cer So­ci­ety es­ti­mates. Typ­i­cal­ly, pa­tients with the ad­vanced form of the dis­ease have lim­it­ed treat­ment op­tions.

The ap­proval was based on the KEYNOTE-181 study, which test­ed the drug ver­sus chemother­a­py in a broad group of 628 pre­vi­ous­ly-treat­ed pa­tients with re­cur­rent lo­cal­ly ad­vanced or metasta­t­ic esophageal can­cer. The main goal of the study — over­all sur­vival — was met on­ly in a sub­group of pa­tients, in pa­tients whose tu­mors ex­press PD-L1.

In its Jan­u­ary up­date, the com­pa­ny said that Keytru­da re­duced the risk of death by 31% in pa­tients with squa­mous cell car­ci­no­ma or ade­no­car­ci­no­ma in the study. The sub­group with PD-L1-pos­i­tive pa­tients — which con­sti­tut­ed 222 pa­tients — achieved a me­di­an OS of 9.3 months ver­sus 6.7 months for the chemother­a­py group. They al­so had a 12-month OS rate of 43% while the chemother­a­py arm ex­pe­ri­enced 20%.

How­ev­er, for the in­ten­tion-to-treat pop­u­la­tion, the dif­fer­ence in OS be­tween the two arms was not sta­tis­ti­cal­ly sig­nif­i­cant. In the 401 pa­tient sub­group of squa­mous cell car­ci­no­ma pa­tients, the Keytru­da group ex­pe­ri­enced a me­di­an OS of 8.2 months, com­pared to 7.1 months for the chemother­a­py arm — an­oth­er non-sta­tis­ti­cal­ly sig­nif­i­cant dif­fer­ence.

Da­ta from the KEYNOTE-180 study, which in­clud­ed 121 pa­tients with lo­cal­ly ad­vanced or metasta­t­ic esophageal can­cer who pro­gressed on or af­ter at least two pri­or sys­temic treat­ments for ad­vanced dis­ease, al­so con­tributed to the ap­proval, Mer­ck said.

Mer­ck $MRK is al­so run­ning a sep­a­rate Phase III study — dubbed KEYNOTE-590 — pit­ting Keytru­da in com­bi­na­tion with chemother­a­py as a first-line treat­ment in pa­tients with esophageal car­ci­no­ma. The tri­al is ex­pect­ed to wrap up next month.

Mean­while, oth­er check­point ri­vals — from Bris­tol-My­ers Squibb $BMY and BeiGene — are lin­ing up to tack­le the no­to­ri­ous­ly hard-to-treat can­cer.

Keytru­da, which is ap­proved for a pletho­ra of can­cers, has ce­ment­ed its crown in the field of im­muno-on­col­o­gy. It gen­er­at­ed $2.6 bil­lion in sec­ond-quar­ter rev­enue, up 58% over the same pe­ri­od a year ago.

The drug is on track to eclipse $10.6 bil­lion in sales by the end of the year — which is more than 50% over what it gen­er­at­ed in 2018 — and to sur­pass $20 bil­lion by 2024, Mizuho an­a­lysts wrote in a note.

Keytru­da was once seen as an un­der­dog to Bris­tol-My­ers’ pi­o­neer­ing Op­di­vo, but a string of tri­al fail­ures left Op­di­vo in the back­seat and Keytru­da as the dri­ving force. Now, some wor­ry that Mer­ck may be lean­ing too heav­i­ly on its key­stone as­set, but the com­pa­ny’s R&D chief Roger Perl­mut­ter is work­ing on but­tress­ing the com­pa­ny’s pipeline with a string of ac­qui­si­tions to mit­i­gate those con­cerns.

“While KEYTRU­DA is grow­ing in dom­i­nance, both in the mar­ket and on MRK’s P&L, we see MRK as hav­ing con­sid­er­able run­way (2028 LOE) to ad­dress con­cerns re­gard­ing con­cen­tra­tion of rev­enue,” Mizuho an­a­lysts added.

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