(Lung Cancer) Atezolizumab Information from ASCO 2017

• July 24, 2017
• 2 min read

This article presents information on atezolizumab for lung cancer. In the Phase III OAK trial, continued use of atezolizumab following RECIST v1.1-defined disease progression in non-small cell lung cancer (NSCLC) resulted in disease control in more than half of patients, with a median post-progression overall survival (OS) exceeding one year.

This report was published at the American Society of Clinical Oncology (ASCO 2017) annual meeting held in Chicago from June 2–6, by Dr. David R. Gandara of the UC Davis Comprehensive Cancer Center in California.

Immune checkpoint inhibitors evaluated by OS, progression-free survival (PFS), and control rates per RECIST v1.1 may underestimate the true clinical value of agents such as atezolizumab.

The primary analysis of the OAK trial compared atezolizumab versus docetaxel (Taxotere) as second- or third-line treatment in 850 NSCLC patients, with an OS hazard ratio (HR) of 0.73 (95% CI: 0.62–0.87), demonstrating a statistically significant OS benefit for atezolizumab. The PFS HR was 0.95 (95% CI: 0.82–1.10), which was not statistically significant.

The POPLAR Phase 2 trial also showed similar inconsistencies with continued post-progression dosing. Dr. Gandara's team used the OAK trial data to evaluate the benefit-risk profile of continuing atezolizumab beyond RECIST v1.1-defined progression.

In the OAK trial, atezolizumab 1200 mg was administered every three weeks. Patients in whom the investigator determined that continued treatment provided clinical benefit could continue beyond progression. The control arm used docetaxel 75 mg/m² every three weeks, also allowing continuation beyond progression. The primary endpoint was OS.

In the atezolizumab arm (n=425) and docetaxel arm (n=425), disease progression was confirmed by RECIST v1.1 in 332 patients (78%) and 290 patients (68%), respectively. The median post-progression OS was 8.6 months in the atezolizumab arm versus 6.4 months in the docetaxel arm, with 18-month OS rates of 26% vs. 18%.

Among the 332 patients who progressed on atezolizumab and continued treatment, 168 (51%) continued atezolizumab with a median of 3 treatment cycles. Complete response (CR) was achieved in 12 patients (7%; defined as ≥30% tumor reduction), while partial response (PR) or stable disease (SD) was seen in 83 patients (49%). Tumor shrinkage was not correlated with PD-L1 expression.

After progression, patients were grouped into three categories: continued atezolizumab (168 patients, 51%), switched to other anticancer agents (94 patients, 28%), and discontinued all anticancer therapy (70 patients, 21%). Baseline characteristics were similar across groups, though ECOG PS differed, with higher proportions of patients with worsening status in the latter groups (18%, 29%, and 33%, respectively).

Regarding disease control rate and median PFS in the post-progression period: continued atezolizumab group: 7.7% and 1.7 months; switched to other anticancer agents: 6.4% and 2.8 months; discontinued treatment: 10.0% and 1.5 months.

Notably, OS outcomes did not align with control rates and PFS. At a median follow-up of 19 months, the median post-progression OS was 12.7 months for the continued atezolizumab group, 8.8 months for patients switched to other agents, and 2.2 months for those who discontinued treatment. The 18-month OS rates were 25% and 8%, respectively. Patients receiving subsequent immunotherapy-based treatment (65 patients, 22%) had a median OS of 17.3 months, compared to 7.5 months for those receiving non-immunotherapy agents (102 patients, 35%), with 18-month OS rates of 37%, 20%, and 9%, respectively.

Based on these clinical results, continued atezolizumab use beyond progression was not associated with increased hazard ratios.

Dr. Gandara noted that this analysis was limited to a non-randomized comparison of the effects of continuing atezolizumab post-progression, and that randomized controlled trials are still needed.

Note: Atezolizumab on Wikipedia: https://en.wikipedia.org/wiki/Atezolizumab

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