Phase III, Randomized Study of Atezolizumab Plus Bevacizumab and Chemotherapy in Patients With EGFR- or ALK-Mutated Non–Small-Cell Lung Cancer (ATTLAS, KCSG-LU19-04)

Author(s): Sehhoon Park, MD, PhD1; Tae Min Kim, MD, PhD2; Ji-Youn Han, MD, PhD3; Gyeong-Won Lee, MD, PhD4; Byoung Yong Shim, MD, PhD5; Yun-Gyoo Lee, MD, PhD6; Sang-We Kim, MD, PhD7; Il Hwan Kim, MD, PhD8; Suee Lee, MD, PhD9; Yu Jung Kim, MD, PhD10; Ji Hyun Park, MD, PhD11; Sang-Gon Park, MD, PhD12; Ki Hyeong Lee, MD, PhD13; Eun Joo Kang, MD, PhD14; Ju Won Kim, MD, PhD15; Seong-Hoon Shin, MD, PhD16; Chan-Young Ock, MD, PhD17; Byung-Ho Nam, PhD18; Jaebong Lee, MS19; Hyun-Ae Jung, MD, PhD1; Jong-Mu Sun, MD, PhD1; Se-Hoon Lee, MD, PhD1; Jin Seok Ahn, MD, PhD1; Myung-Ju Ahn, MD, PhD1
Source: https://doi.org/10.1200/JCO.23.01891
Maem Hussein MD

Dr. Maen Hussein's Thoughts

Adding VEGF inhibitor to PD-1 blocker in addition to chemotherapy is better than a chemotherapy-alone regimen as a second-line therapy after TKI failure. This is true especially in patients with tumors with high PD-L1 expression, with not much besides chemotherapy as second-line therapy for those patients (or other clinical trials) that may be a better option that includes immunotherapy.

PURPOSE

In the treatment of non–small-cell lung cancer (NSCLC) with a driver mutation, the role of anti–PD-(L)1 antibody after tyrosine kinase inhibitor (TKI) remains unclear. This randomized, open-label, multicenter, phase III study evaluates the efficacy of atezolizumab plus bevacizumab, paclitaxel, and carboplatin (ABCP ) in EGFR- or ALK-mutated NSCLC that progressed before TKI therapy.

MATERIALS AND METHODS

We compared the clinical efficacy of ABCP followed by maintenance therapy with atezolizumab plus bevacizumab with pemetrexed plus carboplatin or cisplatin (PC) followed by pemetrexed maintenance. The primary end point was progression-free survival (PFS).

RESULTS

A total of 228 patients with activating EGFR mutation (n = 215) or ALK translocation (n = 13) were enrolled from 16 sites in the Republic of Korea and randomly assigned at 2:1 ratio to either ABCP (n = 154) or PC arm (n = 74). The median follow-up duration was 26.1 months (95% CI, 24.7 to 28.2). Objective response rates (69.5% v 41.9%, P < .001) and median PFS (8.48 v 5.62 months, hazard ratio [HR], 0.62 [95% CI, 0.45 to 0.86]; P = .004) were significantly better in the ABCP than PC arm. PFS benefit increased as PD-L1 expression increased, with an HR of 0.47, 0.41, and 0.24 for PD-L1 ≥1%, ≥10%, and ≥50%, respectively. Overall survival was similar between ABCP and PC arm (20.63 v 20.27 months, HR, 1.01 [95% CI, 0.69 to 1.46]; P = .975). The safety profile of the ABCP arm was comparable with that previously reported, with no additional safety signals, but higher rates of treatment-related adverse events were observed compared with the PC arm.

CONCLUSION

To our knowledge, this study is the first randomized phase III study to demonstrate the clinical benefit of anti–PD-L1 antibody in combination with bevacizumab and chemotherapy in patients with EGFR- or ALK-mutated NSCLC who have progressed on relevant targeted therapy.

Author Affiliations

1Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; 2Department of Internal Medicine, Seoul National University Hospital, Seoul National University Cancer Research Institute, Seoul, Korea; 3Center for Lung Cancer, Research Institute and Hospital, National Cancer Center, Goyang-si Gyeonggi-do, Korea; 4Divisions of Hematology and Oncology, Department of Internal Medicine, Institute of Health Science, Gyeongsang National University Hospital, Gyeongsang National University College of Medicine, Jinju, Korea; 5Division of Medical Oncology, Department of Internal Medicine, St Vincent’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea; 6Division of Hematology & Medical Oncology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea; 7Division of Oncology, Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; 8Department of Internal Medicine, Division of Hemato-Oncology, Haeundae Paik Hospital, Inje University College of Medicine, Busan, Korea; 9Department of Internal Medicine, Dong-A University College of Medicine, Busan, Korea; 10Division of Hematology and Medical Oncology, Department of Internal Medicine, Seoul National University College of Medicine, Seoul National University Bundang Hospital, Seongnam, Korea; 11Department of Hemato-oncololgy, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea; 12Department of Internal Medicine, Hemato-oncology, Chosun University Hospital, Gwangju, Korea; 13Division of Hematology-Oncology, Department of Internal Medicine, Chungbuk National University Hospital, Chungbuk National University College of Medicine, Cheongju, Korea; 14Division of Hematology-Oncology, Department of Internal Medicine, Korea University Guro Hospital, Korea University College of Medicine, Seoul, Korea; 15Divisions of Hematology-Oncology, Department of Medicine, Korea University Anam Hospital, Korea University College of Medicine, Seoul, Korea; 16Division of Hemato-Oncology, Department of Internal Medicine, Kosin University Gospel Hospital, Busan, Korea; 17Lunit, Seoul, Korea; 18Herings, Seoul, Korea; 19Seoul CRO, Seoul, Korea

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