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

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

Amivantamab plus Lazertinib in Previously Untreated EGFR-Mutated Advanced NSCLC

Superior to osi (23 vs 16 progression-free survival). This is more toxic though, but seems manageable. Could this be a new first line standard of care? Also, this includes brain penetration data.

Tyrosine Kinase Inhibitors With and Without Up-Front Stereotactic Radiosurgery for Brain Metastases From EGFR and ALK Oncogene–Driven Non–Small Cell Lung Cancer (TURBO-NSCLC)

Adding SBRT improves local control and disease progression in the brain but not overall survival. Do the radiation oncologists have input? Is it worth it to control symptoms?

Neoadjuvant Osimertinib for the Treatment of Stage I-IIIA Epidermal Growth Factor Receptor–Mutated Non–Small Cell Lung Cancer: A Phase II Multicenter Study

Neoadjuvant Osimertinib did not have a significant impact on major pathologic response and there were no ypCR’s after a median of ~8 weeks of therapy. I do think this shows a measurable response, enough such that I would consider Osi in a patient with “borderline resectable” disease.

Osimertinib after Chemoradiotherapy in Stage III EGFR-Mutated NSCLC

Osimertinib in adjuvant, now after chemotherapy and radiation, next… Neoadjuvant??? Trials are ongoing.

This is here till progression.

Sacituzumab Govitecan Versus Docetaxel for Previously Treated Advanced or Metastatic Non–Small Cell Lung Cancer: The Randomized, Open-Label Phase III EVOKE-01 Study

Failed? Numerical overall survival (OS) benefit for sacituzumab vs docetaxol, but not statistically significant. Better tolerated, also overall survival (OS) noticed more in patients who did not respond to antiPDL-1 therapy.