Continued Atezolizumab After Lung Cancer Progression Might Benefit Patients

Atezolizumab treatment beyond progression (TBP) might benefit patients with advanced non–small-cell lung cancer (NSCLC), according to the first report from the randomized phase III OAK trial (abstract 9001), presented at the 2017 American Society of Clinical Oncology (ASCO) Annual Meeting, held June 2–6 in Chicago.

The findings suggest that RECIST v1.1 (RECIST)-based clinical trial endpoints like overall response rate or progression-free survival could possibly underestimate potential overall survival benefits of cancer immunotherapy with checkpoint inhibitors, argued lead study author David R. Gandara, MD, of the University of California Davis Comprehensive Cancer Center in Sacramento.

The OAK trial research team enrolled 850 patients with advanced or metastatic NSCLC and one or two prior lines of chemotherapy including at least one platinum-based regimen, regardless of PD-L1 status. Patients were randomly assigned 1:1 to receive docetaxel (75 mg/m² every 3 weeks) until disease progression or atezolizumab (1200 mg intravenous every 3 weeks) until disease progression or loss of clinical benefit, Gandara said.

Of 425 patients in the atezolizumab study group, 332 experienced disease progression by RECIST criteria, of whom 168 (51%) continued atezolizumab post-progression, 94 (28%) continued treatment with another non-protocol therapy, and 70 patients (21%) did not continue therapy.

Importantly, patients were not randomly assigned to continue atezolizumab TBP or another treatment after disease progression-a source of selection bias that potentially confounded comparisons between post-treatment subgroups from the atezolizumab and docetaxel study arms, Gandara acknowledged.

Median overall survival for patients who switched or stopped treatment after disease progression was 8.6 months (95% CI, 7–9.9 months) among those in the atezolizumab arm compared with 6.4 months (95% CI, 5.3–7.6 months) among those in the docetaxel arm.

Among the 168 patients who continued atezolizumab therapy after disease progression (atezolizumab TBP), 12 (7%) saw subsequent responses in target lesions, defined as a 30% or greater reduction in tumor after disease progression. Nearly half (49%) had stable target lesions, with tumor reduction or stability observed across all PD-L1 expression subgroups.

After progression, patients who continued atezolizumab treatment had a median overall survival of 12.7 months (95% CI, 9.3–14.9 months), compared with 8.8 months (6–12.1 months) among those treated with other agents and 2.2 months (1.9–3.4 months) among those who did not continue treatment.

Treatment-related adverse events affected 36% of the 168 patients continuing atezolizumab therapy after disease progression (6% grade 3–4), compared with 58.9% prior to disease progression (10.7% grade 3–4).

“Atezolizumab treated beyond progression was not associated with increased safety risk,” concluded Gandara.

The study data suggest atezolizumab TBP is associated with a “positive benefit-risk profile for patients who are performing well clinically” at the time of RECIST disease progression, Gandara said.

However, confirmation will require a randomized clinical trial, he cautioned.

Gandara disclosed consultancy and research funding from Genentech and other drug companies.