WCLC 2018: Early ALTA-1L data encouraging for brigatinib

The ALK- and ROS1-inhibitor brigatinib showed a better progression-free survival (PFS) compared to the ALK-inhibitor crizotinib in the first interim analysis of a head-to-head trial in patients with ALK-positive non-small cell lung cancer (NSCLC) who hadn’t yet received an ALK-inhibitor, researchers said here in the Plenary at the IASLC 19th World Congress on Lung Cancer.

By Thomas R Collins / Interviews by Esther Drain.

Professor Ross Camidge (Denver, USA), Dr Sanjay Popat (London, UK)

ALTA-1: First line brigatinib vs crizotinib in ALK+ NSCLC

At 99 progression events— the scheduled point for the analysis in the ALTA-1L trial, which has enrolled 275 patients — 36% of those in the brigatinib group had experienced an event, compared to 63% in the crizotinib group, yielding a hazard ratio (HR) for progression or death of 0.49 for brigatinib (p=.0007).

Among those with any brain metastases at baseline, the PFS HR was 0.27 (p<.0001), with median intracranial PFS not reached in the brigatinib arm and 5.6 months in the crizotinib arm in those patients. As brain metastases are a significant concern in ALK+ NSCLC, the activity of brigatinib seen so far in ALTA1 is very promising.

Overall, the median PFS was not reached in the brigatinib arm and was 9.2 months in the crizotinib arm. Investigators noted that brigatinib was well-tolerated, with dose reductions mandated by the protocol for asymptomatic lab abnormalities including creatine phosphokinase, lipase and liver function.

“Brigatinib represents a promising new first-line treatment option for ALK-positive NSCLC,” said Professor Ross Camidge, who presented the findings and is director of thoracic oncology at the University of Colorado.

http://vimeo.com/293643038

Dr Robert Doebele (Aurora, USA), Dr Sanjay Popat (London, UK), Dr Natasha Leighl (Toronto, Canada),Dr Thomas Newsom-Davis (London, UK), Dr Riyaz Shah (Maidstone, UK)

ALTA 1: implications for first line ALK TKIs

Professor Fiona Blackhall, at the University of Manchester, said brigatinib joins crizotinib, alectinib and ceritinib as a front-line option in these patients. But she said it’s too soon to tell whether it will prove to be a better option than alectinib, which has been shown to have a median PFS of 34.8 months at a median follow-up of 27.8 months, compared to ALTA-1L’s median follow-up of 11 months.

Although the early first interim analysis is highly provocative, the median follow-up is substantially less,” she said. “And further follow-up will be needed to determine how close or whether indeed brigatinib can even beat alectinib in progression-free survival.” More follow-up is also needed to gauge how brigatinib compares in terms of brain metastases, she said.

She noted that it’s a “frustration,” in both ALTA-1L and the alectinib’s ALEX trial, that translational information wasn’t collected on the mutations at progression, given that an important question is whether the choice of first-line ALK-inhibitor has an effect on resistant mutations. She also questioned whether crizotinib as a control arm is “really relevant” in ongoing clinical trials.

In a poster presentation, researchers at Otto Wagner Hospital in Vienna reported that brigatinib produced a high rate of response as second- or third-line therapy among patients with EML4-ALK-rearranged NSCLC.  Three of the 35 patients had a complete response, 25 had a partial response and 5 had disease progression. The median PFS was 7.5 months and treatment of 21 patients was ongoing.

Dr Thomas Newsom-Davis (London, UK), Dr Alastair Greystoke (Newcastle, UK)

UK research: brigatinib real world data

In another poster, researchers at University Hospitals Leicester in England, who are tracking treatment of ALK-positive patients at medical centres across the country, reported that 14 of the 28 patients who’d received brigatinib at any point in their treatment had an objective response on the drug. The median exposure time overall was 12.1 and in the first- and second-line settings the ORR was 69%.

Six patients had received the drug in as first-line therapy; 7 as second-line; 8 as third-line; and 9 as fourth- or fifth-line.

Despite being used mainly in heavily pre-treated patients,” researchers said, “our data confirm a meaningful clinical benefit.”