Immuno/Chemo/Bev Combo 'Promising' in Advanced Lung Cancer

Nick Mulcahy

December 11, 2017

A combination approach that includes immunotherapy for the initial treatment of advanced lung cancer improved progression-free survival (PFS) compared with using just chemotherapy, according to new data from a multiarm trial presented at ESMO Immuno Oncology Congress 2017 in Geneva, Switzerland.

"This is the first phase III trial to report on the combination of chemotherapy, antiangiogenic treatment and immunotherapy as first-line treatment for advanced non-squamous cell non-small-cell lung cancer," said lead author, Professor Martin Reck, from the Lung Clinic Grosshansdorf in Germany, in a press statement.

Dr Reck explained that the trial, known as IMpower 150, randomly assigned 1202 patients to one of three groups: chemotherapy plus the immunotherapy atezolizumab (Tecentriq, Roche); a triple therapy consisting of those two elements plus the antiangiogenic bevacizumab (Avastin, Roche); or chemotherapy plus bevacizumab.

Atezolizumab acts by inhibiting the programmed death ligand 1 (PD-L1). The chemotherapy was carboplatin plus paclitaxel.

For the co-primary endpoint of PFS, the triple therapy combination demonstrated a superior median PFS compared with bevacizumab plus chemotherapy (8.3 vs 6.8 months; hazard ratio [HR], 0.62; P < .0001) in the intention-to-treat "wild-type" subpopulation. This excluded any patients with EGFR mutations or ALK rearrangements because these patients are treated with targeted drugs.

The investigators also reported results for a subgroup of patients with defined expression of a T-effector gene signature in the tumor tissue (Teff-WT patients), and in this subgroup the PFS was also significantly longer  with the triple combination than with the combination of bevacizumab plus chemotherapy (11.3 vs 6.8 months; HR, 0.51; P < .0001).

Notably, in this latter comparison, the PFS benefit occurred regardless of PD-L1 status.

The triple combination has not yet been tested against chemotherapy plus immunotherapy because of a prespecified testing hierarchy, the researchers note.

"The results show there is a way to improve the efficacy of platinum-based chemotherapy" in this setting, said Dr Reck, and he described the triple therapy's improvement in PFS as "clinically relevant."

He also pointed out that there were no new safety issues with the triple combination. Treatment-related serious adverse events were 25% in the patients receiving the  immunotherapy/angiogenesis treatment/chemotherapy combination vs 19% among those receiving the bevacizumab plus chemotherapy combination.

The study results were impressive enough that an expert not involved with the study said they could eventually change practice.

Professor Solange Peters from the Centre Hospitalier Universitaire Vaudois in Lausanne, Switzerland, who acted as discussant for the study at the meeting, said, "These exciting results pave the way for a new standard of care in advanced nonsquamous, non-small cell lung cancer."

Dr Peters made multiple other comments that placed that projection in an appropriate context.

First, she observed that immunotherapy is the current standard treatment in this setting for patients who do not have targetable mutations --- after platinum-based chemotherapy. But immunotherapy and chemotherapy, in combination, are also approved by the US Food and Drug Administration for initial use in unselected patients with nonsquamous non-small cell lung cancer (ie, those without PD-L1 selection). That approval in 2016 came from a phase 2 trial, based on positive response rates, as reported at the time by Medscape Medical News.

Thus, IMpower150 is the first phase 3 randomized trial to compare the combination of immunotherapy plus chemotherapy vs chemotherapy in the frontline setting, she said, echoing Professor Reck's comments.

This is very, very promising. Dr Solange Peters

Dr Peters continued and said that the benefit of immunotherapy is sometimes delayed and that later time points may be more encouraging. "When you look at the 12-month PFS, you double the number of patients who have not progressed from 18% without immunotherapy to 37% when you add the immunotherapy," she said in a meeting press statement. "This is very, very promising. Doubling PFS at one year is something we have not seen with any targeted therapy in unselected patients."

Results on overall survival, which is the other co-primary endpoint, are awaited, but the initial findings are "encouraging," she added.

The study was funded by Roche. Dr Reck has financial relationships with multiple pharmaceutical companies, including Roche. Multiple study authors are Roche employees.

ESMO Immuno Oncology Congress 2017. LBA1. Presented December 7.

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