Atezolizumab added to chemo ups survival in lung cancer

By David Douglas

NEW YORK (Reuters Health) - 31/5/2019

As first-line treatment for metastatic non-squamous non-small-cell lung cancer (NSCLC), the anti-PD-L1 agent atezolizumab (Tecentriq, Genentech) in combination with chemotherapy boosts survival compared with chemotherapy alone, according to a company-funded study.

Dr. Federico Cappuzzo told Reuters Health by email that in the study "chemotherapy consisted of carboplatin and nab-paclitaxel that is a different formulation of paclitaxel not requiring steroids premedication that could potentially interfere with immunotherapy efficacy."

For their study, online May 20 in The Lancet Oncology, Dr. Cappuzzo of AUSL Romagna, in Ravenna, Italy, and colleagues randomly assigned patients 2:1 to chemotherapy along with atezolizumab or to chemotherapy alone.

Co-primary endpoints were investigator-assessed progression-free survival and overall survival in randomized patients with EGFRwt or ALKwt tumors (that is, the wild-type population).

In total, 451 patients in the combination group were included in the intention-to-treat wild-type population and 483 altogether in the intention-to treat population. The chemotherapy group included 228 in the intention-to-treat wild-type population and 240 altogether were included in intention-to-treat analysis. Median follow-up (of about 19 months) was similar in both groups.

In the intention-to-treat wild-type population, there were significant improvements in median overall survival in the combination group compared with those on chemotherapy alone (18.6 vs. 13.9 months). This was also the case for progression-free survival (7.0 vs. 5.5 months).

Subgroup analyses showed consistent overall benefit with atezolizumab across the majority of clinical subgroups. However, overall survival was not improved in patients with liver metastases or in those with EGFR or ALK genomic alterations.

Treatment-related serious adverse events were reported in 24% of the combination group and 13% of patients in the chemotherapy group.

Twenty-six percent of patients on combination treatment left any study treatment due to adverse events versus 22% of those on chemotherapy alone.

There were 25 deaths (5%) among the 473 patients on atezolizumab plus chemotherapy and 13 (6%) among the 232 patients in the chemotherapy group. Deaths related to any treatment component, as judged by investigators, occurred in 1.7% and 0.4%, respectively.

"The study showed a significant prolongation in overall survival for patients receiving the combination of immunotherapy and chemotherapy," Dr. Cappuzzo concluded. "These results confirm that chemoimmunotherapy is the new standard of care in patients with metastatic NSCLC."

In an accompanying editorial, Dr. Yangqiu Li of Jinan University and Dr. Yi-Long Wu of Guangdong Lung Cancer Institute, both in Guangzhou, China, note, "Overall, atezolizumab in combination with carboplatin plus nab-paclitaxel is an efficacious and a safe regimen and might be an additional treatment option for stage IV non-squamous non-small-cell lung cancer."

The study was funded by F. Hoffmann-La Roche. Genentech is a member of the Roche Group and a number of authors including Dr. Cappuzzo have relationships with these companies and six are employees.


Lancet Oncol 2019.

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