ESMO: Roche eyes untouched newly diagnosed lung cancer market for solo Tecentriq

Merck’s Keytruda has long established itself as the standard of care in newly diagnosed non-small cell lung cancer (NSCLC). But now, Roche aims to carve out a market for Tecentriq by targeting a neglected group of patients.

The unique market Roche has spotted covers patients with advanced NSCLC who cannot tolerate platinum-based chemotherapy. In these patients, Tecentriq monotherapy cut the risk of death by 22% against chemo, according to data from the phase 3 IPSOS trial presented at the European Society for Medical Oncology (ESMO) congress 2022.

IPSOS is the first randomized trial to show that Tecentriq can improve life expectancy over chemo for these first-line patients who, because of poor health status, are often excluded from clinical trials, study first author Siow Ming Lee at University College London said in a statement facilitated by ESMO.

In the trial, Tecentriq demonstrated life extension benefits regardless of patients’ age, cancer subtypes, PD-L1 status or performance status as measured by the ECOG score, Lee added.

“[Roche’s] team is looking at potential filing options, because there’s no question—we think this is an important contribution to clinical care, and we would welcome making that available to patients,” Charlie Fuchs, M.D., global head of oncology and hematology drug development at Roche’s Genentech, said in an interview with Fierce Pharma ahead of the data presentation.

Tecentriq and Keytruda are both approved as single agents to treat newly diagnosed NSCLC patients with high expression of the PD-L1 biomarker. But the clinical trials that supported the approvals—Tecentriq’s IMpower110 and Keytruda’s KEYNOTE-024—enrolled patients with good performance status scores at ECOG 0 or 1. Patients with poor status have often been excluded in other major clinical trials involving PD-1/L1 inhibitors or cancer clinical trials in general.

Still, more than 40% of patients in the advanced stage 3b to IV NSCLC population suffer from poor performance status—with ECOG scores of 2 and above—or are elderly people with multiple comorbidities who can’t tolerate platinum-based chemo, according to Lee.

IPSOS enrolled 453 platinum-ineligible patients aged 70 or older with ECOG scores of at least 2 or underlying health issues. At two years, twice as many patients on Tecentriq were estimated to be alive than those on chemo, according to the investigators. The two-year survival rates were 24.3% and 12.4%, respectively.

But in a relatively disappointing showing, Tecentriq only extended the median time the patients had lived by merely 1.1 months compared with chemo to 10.3 months.

In clinical trials, cancer immunotherapies’ survival benefits tend to only start showing toward the midpoint of advancement toward the death event endpoint, Fuchs said. So, the Roche exec argued that death risk reduction—by assessing the entire difference between the two treatments’ patient survival trajectories as opposed to one point—captures the “full nature” of the drug's benefit.

Besides efficacy, Tecentriq was associated with fewer grade 3 or 4 treatment-related side effects at 16.3% compared with chemo’s 33.3%. Side effects also caused 1% of deaths in the Tecentriq arm, versus 2.7% in the chemo group.

Investigators also linked the Roche PD-L1 inhibitor to some quality of life gains. The med cut the risk of chest pain by 49% and offered “meaningful improvements” in appetite loss and cough, researchers said.

While Tecentriq monotherapy might be looking at a niche front-line NSCLC field, all eyes are currently on the drug’s experimental combination with Roche’s TIGIT inhibitor tiragolumab. The pairing recently failed to show a significant improvement over Tecentriq monotherapy at stalling tumor progression in first-line PD-L1-high NSCLC. But Roche also spotted a numeric improvement in patient survival, leaving hope that the regimen might eventually turn out successful.

Roche is now continuing that closely watched SKYSCRAPER-01 trial and plans to provide more mature overall survival data in 2023, Fuchs said, declining to narrow down that timeline.