Lung can­cer pa­tients liv­ing longer with im­mune ther­apy

Ex­perts say new study should spur im­me­di­ate changes.

Austin American-Statesman - - MORE OF TODAY’S TOP NEWS - Denise Grady ©2018 The New York Times

The odds of sur­vival can greatly im­prove for peo­ple with the most com­mon type of lung can­cer if, along with the usual chemo­ther­apy, they are also given a drug that ac­ti­vates the im­mune sys­tem, a ma­jor new study has shown.

The find­ings should change med­i­cal prac­tice im­me­di­ately, can­cer ex­perts say: Pa­tients with this type of lung can­cer should re­ceive an im­mune-ac­ti­vat­ing drug, also called im­munother­apy, as early as pos­si­ble af­ter the di­ag­no­sis is made.

“What it sug­gests is that chemo­ther­apy alone is no longer a stan­dard of care,” said Dr. Leena Gandhi, a leader of the study and di­rec­tor of the Tho­racic Med­i­cal On­col­ogy Pro­gram at the Perl­mut­ter Can­cer Cen­ter at New York Univer­sity Lan­gone Health.

The find­ings rep­re­sent an­other step for­ward for im­munother­apy, which has been mak­ing steady gains against a num­ber of dif­fer­ent can­cers. Four im­munother­apy drugs for can­cer, known as check­point in­hibitors, have been ap­proved. The drugs un­leash the pa­tient’s im­mune sys­tem to kill ma­lig­nant cells.

They cost more than $100,000 a year, can have se­ri­ous side ef­fects and help only some pa­tients, gen­er­ally fewer than half. But when the drugs work, re­sponses can be long-last­ing, and re­searchers are rush­ing to find ways to com­bine treat­ments to im­prove their ef­fects and to de­ter­mine which for­mu­la­tion is best for each pa­tient.

“I’ve been treat­ing lung can­cer for 25 years now, and I’ve never seen such a big par­a­digm shift as we’re see­ing with im­munother­apy,” said Dr. Roy Herbst, chief of Med­i­cal On­col­ogy at the Yale Can­cer Cen­ter. He was not in­volved in the study.

Lung can­cer is the lead­ing cause of can­cer death glob­ally, caus­ing 1.7 mil­lion deaths a year. It is ex­pected to kill more than 154,000 peo­ple in the U.S. in 2018.

Pa­tients in the study had an ad­vanced stage of non-squa­mous non-small-cell l ung can­cer. The im­mune-ac­ti­vat­ing drug was a check­point in­hibitor called pem­brolizumab, or Keytruda, made by Merck, which paid for the study. The chemo­ther­apy was a drug called peme­trexed, plus ei­ther car­bo­platin or cis­platin.

Gandhi said chemo­ther­apy alone had only a “mod­est ben­e­fit,” and could add only a few months of life, with most pa­tients sur­viv­ing about a year or less. The com­bi­na­tion treat­ment is a sig­nif­i­cant im­prove­ment, she said. It is al­ready ap­proved as a first-line treat­ment for this dis­ease, so it should be cov­ered by health in­sur­ers.

She was sched­uled to present the re­sults Mon­day in Chicago at a meet­ing of the Amer­i­can As­so­ci­a­tion for Can­cer Re­search, and they were also pub­lished in The New Eng­land Jour­nal of Medicine.

Other stud­ies pre­sented at the meet­ing also high­lighted ad­vances in im­munother­apy against lung can­cer, but were at ear­lier points in the re­search and less likely to bring about im­me­di­ate changes in med­i­cal prac­tice.

“If you want to see longterm sur­vival, you’ve got to give im­munother­apy as soon as pos­si­ble,” Herbst said. “Chemo­ther­apy has lim­i­ta­tions.Im­munother­a­py­has­the abil­ity to cure. I lead the Yale lung team. We have pa­tients on these im­munother­a­pies alive more than eight years.”

Other stud­ies in lung can­cer have in­volved an­other check­point in­hibitor, nivolumab, or Op­divo (made by Bris­tol-My­ers Squibb), which works in a sim­i­lar way to pem­brolizumab. The data are not con­clu­sive, but Herbst said, “In lung can­cer, my sus­pi­cion is these drugs are the same, like Coke vs. Pepsi.”

Most pa­tients stay on the drugs two years, he said. One Yale pa­tient who has sur­vived for eight years took the drug for two years and has re­mained well ever since. An­other had to stop be­cause of side ef­fects af­ter only two or three months, but is still well two years later.

Herbst of­fered sev­eral the­o­ries about why chemo­ther­apy and im­munother­apy work well to­gether. He said tu­mor cells were like bags of hid­den proteins that, if ex­posed, the im­mune sys­tem could use as tar­gets to find and at­tack can­cer. By killing some tu­mor cells, chemo­ther­apy could pop open the bags, re­lease the con­tents and help im­mune cells iden­tify their prey. It is also pos­si­ble, he said, that chemo­ther­apy may kill some im­mune cells that in­ter­fere with the can­cer-killing ac­tion of other parts of the im­mune sys­tem.

Gandhi’s study in­cluded 616 pa­tients with ad­vanced lung can­cer, from med­i­cal cen­ters in 16 coun­tries. Their tu­mors lacked cer­tain mu­ta­tions that would have made them el­i­gi­ble for other, “tar­geted” treat­ments. They were picked at ran­dom to re­ceive ei­ther chemo­ther­apy plus im­munother­apy, or chemo­ther­apy plus a placebo, with two-thirds re­ceiv­ing the com­bi­na­tion that in­cluded im­munother­apy.

Af­ter a me­dian fol­low-up of 10.5 months, those i n the im­munother­apy group were half as likely to die. The me­dian over­all sur­vival was 11.3 months in those who did not re­ceive im­munother­apy, whereas sur­vival in the im­munother­apy group was longer and the me­dian has not yet been reached.

But pa­tients in the im­munother­apy group had more kid­ney prob­lems, more im­mune-re­lated ad­verse events and were more likely to stop treat­ment be­cause of side ef­fects.

The es­ti­mated sur­vival at 12 months was 69.2 per­cent in the group that re­ceived im­munother­apy, and 49.4 per­cent in those who did not.

GE­ORGE ETHEREDGE / THE NEW YORK TIMES 2017

Bruce Fen­ster­ma­cher meets with Dr. Was­sim Abida at the Memo­rial Sloan Ket­ter­ing Can­cer Cen­ter in New York. A new study finds pa­tients with the most com­mon type of lung can­cer have bet­ter sur­vival rates when given an im­munother­apy drug along with their...

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