M. Gandhi

Updated Efficacy Analysis Including Secondary Population Results for OAK: A Randomized Phase III Study of Atezolizumab versus Docetaxel in Patients with Previously Treated Advanced Non–Small Cell Lung Cancer

Introduction: The efficacy and safety of atezolizumab versus the efficacy and safety of docetaxel as second‐ or third‐line treatment in patients with advanced NSCLC in the primary (n = 850) and secondary (n = 1225) efficacy populations of the randomized phase III OAK study (respectively referred to as the intention‐to‐treat [ITT] 850 [ITT850] and ITT1225) at an updated data cutoff were assessed. Methods: Patients received atezolizumab, 1200 mg, or docetaxel, 75 mg/m2, intravenously every 3 weeks until loss of clinical benefit or disease progression, respectively. The primary end point was overall survival (OS) in the ITT population and programmed death‐ligand 1–expressing subgroup. A sensitivity analysis was conducted to evaluate the impact of subsequent immunotherapy use in the docetaxel arm on the observed survival benefit with atezolizumab. Results: Atezolizumab demonstrated an OS benefit versus docetaxel in the updated ITT850 (hazard ratio [HR] = 0.75, 95% confidence interval: 0.64–0.89, p = 0.0006) and the ITT1225 (HR = 0.80, 95% confidence interval: 0.70–0.92, p = 0.0012) after minimum follow‐up times of 26 and 21 months, respectively. Improved survival with atezolizumab was observed across programmed death‐ligand 1 and histological subgroups. In the immunotherapy sensitivity analysis, the relative OS benefit with atezolizumab was slightly greater in the ITT850 (HR = 0.69) and ITT1225 (HR = 0.74) than the conventional OS estimate. Fewer patients receiving atezolizumab experienced grade 3 or 4 treatment‐related adverse events (14.9%) than did patients receiving docetaxel (42.4%); no grade 5 adverse events related to atezolizumab were observed. Conclusions: The results of the updated ITT850 and initial ITT1225 analyses were consistent with those of the primary efficacy analysis demonstrating survival benefit with atezolizumab versus with docetaxel. Atezolizumab continued to demonstrate a favorable safety profile after longer treatment exposure and follow‐up.

Severe adverse events impact overall survival and costs in elderly patients with advanced non-small cell lung cancer on second-line therapy

OBJECTIVES Elderly patients with advanced non-small lung cancer (aNSCLC) represent a high-risk patient population due to disease burden, comorbidities, and performance status, particularly after progressing on first-line therapy. Among elderly patients who receive second-line therapy, treatment related toxicities can have substantial impact on both clinical and economic outcomes. This study assessed the impact of severe adverse events (AEs) during second-line therapy on overall survival (OS) and all-cause heathcare costs in elderly with aNSCLC. MATERIALS AND METHODS Patients with aNSCLC aged ≥65 years who initiated second-line chemotherapy/targeted therapy were identified in the SEER-Medicare database (2007-2011). Fifty-seven AEs were identified by literature review and consultation with two oncologists. Severe AEs were defined as AEs that required a hospitalization and were operationalized based on AE diagnosis(es) recorded during hospitalizations. OS post-second-line initiation and healthcare costs during second-line were compared between patients with and without severe AEs. RESULTS Among 3967 patients initiating second-line therapy, 1624 (41%) had ≥1 severe AE, where hypertension (26%), anemia (24%), and pneumonia (23%) were most commonly reported. Patients with and without severe AEs had similar demographic and cancer characteristics at diagnosis and similar second-line treatment regimens, but patients with severe AEs had more comorbidities at second-line initiation. Median OS was lower in patients with versus without severe AEs (6 vs. 11 months). After multivariate adjustment, hazard of death was more than twice higher in patients with versus without severe AEs (adjusted hazard ratio [HR] 2.31, 95% CI 2.16-2.47). Healthcare costs were more than twice higher in patients with versus without severe AEs (

Atezolizumab Treatment Beyond Progression in Advanced Non-Small Cell Lung Cancer: Results From the Randomized, Phase III OAK Study

16,135 vs.

Impact of atezolizumab (atezo) treatment beyond disease progression (TBP) in advanced NSCLC: Results from the randomized phase III OAK study.

7559 per-patient-per-month). CONCLUSION Severe AEs among elderly patients with aNSCLC treated with second-line chemotherapy/targeted therapy were found to be associated with decreased OS and increased healthcare costs. Results suggest a potential link between severe AEs in second-line treated aNSCLC elderly and patient survival and economic burden to the healthcare system.

81OSafety and efficacy analyses of atezolizumab in advanced non-small cell lung cancer (NSCLC) patients with or without baseline brain metastases

Introduction: Cancer immunotherapy may alter tumor biology such that treatment effects can extend beyond radiographic progression. In the randomized, phase III OAK study of atezolizumab (anti–programmed death‐ligand 1) versus docetaxel in advanced NSCLC, overall survival (OS) benefit with atezolizumab was observed in the overall patient population, without improvement in objective response rate (ORR) or progression‐free survival (PFS). We examine the benefit‐risk of atezolizumab treatment beyond progression (TBP). Methods: Eight hundred fifty patients included in the OAK primary efficacy analysis were evaluated. Atezolizumab was continued until loss of clinical benefit. Docetaxel was administered until Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1) disease progression (PD)/unacceptable toxicity; no crossover to atezolizumab was allowed. ORR, PFS, post‐PD OS, target lesion change, and safety were evaluated. Results: In atezolizumab‐arm patients, ORR was 16% versus 14% and median PFS was 4.2 versus 2.8 months per immune‐modified RECIST versus RECIST v1.1. The median post‐PD OS was 12.7 months (95% confidence interval [CI]: 9.3–14.9) in 168 atezolizumab‐arm patients continuing TBP, 8.8 months (95% CI: 6.0–12.1) in 94 patients switching to nonprotocol therapy, and 2.2 months (95% CI: 1.9–3.4) in 70 patients receiving no further therapy. Of the atezolizumab TBP patients, 7% achieved a post‐progression response in target lesions and 49% had stable target lesions. Atezolizumab TBP was not associated with increased safety risks. Conclusions: Within the limitations of this retrospective analysis, the post‐PD efficacy and safety data from OAK are consistent with a positive benefit‐risk profile of atezolizumab TBP in patients performing well clinically at the time of PD.