Adding a second pill held off advanced lung cancer for longer

Two growth switches, two pills

Lung cancer kills more people than any other cancer. On October 26, the drug maker HUTCHMED shared positive results from a large study in China. Yi-Long Wu, who led the study, presented them at a major cancer meeting in Madrid.

Every patient had advanced lung cancer driven by a growth switch in tumor cells that was stuck on. It kept telling the cells to grow. Their tumors also made far too much of a second growth switch, a protein that tells cells to grow. All took the usual daily pill against the first switch; half also took a pill against the second, the rest a dummy pill. With both pills, the typical patient went more than two years before the cancer grew again. With the usual pill alone, it was about a year.

A second road for the tumor, and a stain that finds it

A targeted pill is built to block one specific switch. The usual pill, osimertinib, blocks the first one. The second switch is MET, a protein that also tells cells to grow. When a tumor makes too much of it, the growth signal takes another road around the blocked first switch. The added pill, savolitinib, closes that road.

Finding the right patients takes a lab test that stains a thin slice of tumor to show how much MET the cells carry. The stain test gives each tumor a score. The top score, 3+, means at least 90% of the tumor cells stain strongly. The lower score, 2+, means less MET, but still more than normal. To find people who could take part in the study, the team tested 1,896 people. Of those, 326 met the study's rules.

The score mattered. Among patients with the top score, the typical one on both pills went 24.8 months before the cancer grew. On the usual pill alone, it was 11.1 months. For the 2+ patients, the gain was smaller and too shaky to rule out pure chance. The gain also looked bigger when the cancer had spread to the brain, but such small-group results are only hints. Holding the cancer back is one thing. Did people also live longer?

Longer lives so far, with the count still running

They did, at least so far. With both pills, the number of patients still alive fell to half after 44.5 months. With the usual pill alone, this took 34.9 months. The study also counted how many patients were alive after three years. With both pills, 67.4% were alive then. With the usual pill alone, 47.4% were alive.

The count is not finished, though. By then, 49 people on both pills had died, against 83 on the usual pill alone. So far, only 40.5% of the deaths expected during the study had occurred. The figures for how long people lived can still change as the count continues. No formal test checked whether the gap between the groups could be due to chance. And a longer life counts for more when the extra pill is bearable.

Swollen ankles and more severe side effects

Almost everyone had some side effect: all of those on both pills, and 99.4% on the usual pill alone. Severe or worse side effects hit 77.2% of people taking both pills. They hit 38.4% of those taking the usual pill alone. Serious side effects are the kind that send people to the hospital. These hit 54.9% of people taking both pills. They hit 28.7% of those taking the usual pill alone. HUTCHMED says only 14.8% of patients taking both pills stopped treatment because of side effects. With the usual pill alone, 4.3% stopped for that reason. That makes "only" a generous word.

The most common problem was swelling, mostly in the legs and ankles. It hit 65% of people on both pills, but just 7% on the single pill. HUTCHMED says changing the dose kept most side effects in check. Deaths from side effects, though, were low and about even between the groups. So who can actually get these pills today?

Approved later in China, not yet first anywhere

In China, doctors can already give the two pills together, but only later on. That use is for patients whose cancer kept growing on pills against the first switch. Their tumors must also carry extra copies of the MET gene, the instructions for making MET. This means extra gene copies, not just a high score on the stain test. No country has approved the pair as a first treatment. Switzerland allows it for now, but only after the usual pill has stopped working. HUTCHMED next plans to ask Chinese regulators to approve both pills together as a first treatment. It has named no such request anywhere else, and in the US the added pill is not approved for any use.

Two questions stay open. Every patient was treated in China, so the gain still has to show up elsewhere. Rebecca Heist, an outside expert asked to comment on the study, raised another question. What MET stain score should patients need to get both pills from the start of treatment?

I like the plan of closing the second road before the tumor can use it. It treats the cancer as something that adapts, which it is. So with two roads closed, which one will it try next? Heist asked that too, and to me it decides how long this gain lasts.