Nivolumab Plus Chemotherapy in Epidermal Growth Factor Receptor–Mutated Metastatic Non–Small-Cell Lung Cancer After Disease Progression on Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors: Final Results of CheckMate 722

Author(s): Tony Mok, MD, FRCPC, FASCO¹; Kazuhiko Nakagawa, MD, PhD²; Keunchil Park, MD, PhD^3,4; Yuichiro Ohe, MD, PhD⁵; Nicolas Girard, MD⁶; Hye Ryun Kim, MD, PhD⁷; Yi-Long Wu, MD⁸; Justin Gainor, MD⁹; Se-Hoon Lee, MD, PhD³; Chao-Hua Chiu, MD^10,11; Sang-We Kim, MD, PhD¹²; Cheng-Ta Yang, MD¹³; Chien Liang Wu, MD¹⁴; Lin Wu, MD¹⁵; Meng-Chih Lin, MD¹⁶; Jens Samol, MD^17,18; Kazuya Ichikado, MD¹⁹; Mengzhao Wang, MD²⁰; Xiaoqing Zhang, MD, PhD²¹; Judi Sylvester, BS²¹; Sunney Li, PhD²¹; Ann Forslund, PhD²¹; James Chih-Hsin Yang, MD, PhD²²

Source: https://doi.org/10.1200/JCO.23.01017

Dr. Maen Hussein's Thoughts

This is the same issue as the 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) article, this one was negative though. A question for the previous trial would be: do we need PDL-1 inhibitor, or just VEGF inhibitor, recall the pts with tumors with high PDL-1 expression did better though, so most likely we need both with chemotherapy.

PURPOSE

The phase III CheckMate 722 trial (ClinicalTrials.gov identifier: NCT02864251) evaluated nivolumab plus chemotherapy versus chemotherapy in patients with epidermal growth factor receptor (EGFR)–mutated metastatic non–small-cell lung cancer (NSCLC) after disease progression on EGFR tyrosine kinase inhibitors (TKIs).

METHODS

Patients with disease progression after first- or second-generation EGFR TKI therapy (without EGFR T790M mutation) or osimertinib (with/without T790M mutation) were randomly assigned 1:1 to nivolumab (360 mg once every 3 weeks) plus platinum-doublet chemotherapy (once every 3 weeks) or platinum-doublet chemotherapy alone (once every 3 weeks) for four cycles. Primary end point was progression-free survival (PFS). Secondary end points included 9- and 12-month PFS rates, overall survival (OS), objective response rate (ORR), and duration of response (DOR).

RESULTS

Overall, 294 patients were randomly assigned. At final analysis (median follow-up, 38.1 months), PFS was not significantly improved with nivolumab plus chemotherapy versus chemotherapy (median, 5.6 v 5.4 months; hazard ratio [HR], 0.75 [95% CI, 0.56 to 1.00]; P = .0528), with 9- and 12-month PFS rates of 25.9% versus 19.8%, and 21.2% versus 15.9%, respectively. Post hoc PFS subgroup analyses showed a trend favoring nivolumab plus chemotherapy in patients with tumors harboring sensitizing EGFR mutations (HR, 0.72 [95% CI, 0.54 to 0.97]), one line of previous EGFR TKI (0.72 [95% CI, 0.54 to 0.97]), or both (0.64 [95% CI, 0.47 to 0.88]). Median OS was 19.4 months with nivolumab plus chemotherapy versus 15.9 months with chemotherapy, while ORR was 31.3% versus 26.7%, and median DOR was 6.7 versus 5.6 months, respectively. Grade 3/4 treatment-related adverse events occurred in 44.7% and 29.4% of patients treated with nivolumab plus chemotherapy and chemotherapy alone, respectively.

CONCLUSION

Nivolumab plus chemotherapy did not significantly improve PFS versus chemotherapy in patients with EGFR-mutated metastatic NSCLC previously treated with EGFR TKIs. No new safety signals were identified.

Author Affiliations

¹State Laboratory of Translational Oncology, The Chinese University of Hong Kong, Hong Kong, China; ²Kindai University Faculty of Medicine, Osaka, Japan; ³Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea; ⁴University of Texas MD Anderson Cancer Center, Houston, TX; ⁵National Cancer Center Hospital, Tokyo, Japan; ⁶Institut du Thorax Curie-Montsouris, Institut Curie, Paris, France; ⁷Division of Medical Oncology, Department of Internal Medicine, Yonsei Cancer Center, Yonsei University College of Medicine, Seoul, Korea; ⁸Guangdong Lung Cancer Institute, Guangdong Province People’s Hospital (Guangdong Academy of Medical Sciences), Southern Medical University, Guangzhou, China; ⁹Massachusetts General Hospital, Harvard Medical School, Boston, MA; ¹⁰Taipei Veterans General Hospital, Taipei City, Taiwan; ¹¹Taipei Cancer Center, Taipei Medical University Hospital, Taipei Medical University, Taipei City, Taiwan; ¹²Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea; ¹³Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, Taiwan; ¹⁴Mackay Memorial Hospital, Taipei, Taiwan; ¹⁵Hunan Cancer Hospital, Changsha, China; ¹⁶Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, Kaohsiung City, Taiwan; ¹⁷Tan Tock Seng Hospital, Lee Kong Chian School of Medicine, Singapore, Singapore; ¹⁸Johns Hopkins University, Baltimore, MD; ¹⁹Saiseikai Kumamoto Hospital, Kumamoto, Japan; ²⁰Peking Union Medical College Hospital, Beijing, China; ²¹Bristol Myers Squibb, Princeton, NJ; ²²National Taiwan University Cancer Center, National Taiwan University Hospital, Taipei City, Taiwan

Ivonescimab Plus Chemotherapy in Non–Small Cell Lung Cancer With EGFR Variant – A Randomized Clinical Trial

Bispecific (a bispecific antibody targeting programmed cell death 1 protein and vascular endothelial growth factor) and chemotherapy … and it worked … second line after EGFR therapy failure.

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.

Phase II Efficacy and Safety of 80 mg Osimertinib in Patients With Leptomeningeal Metastases Associated With Epidermal Growth Factor Receptor Mutation–Positive Non–Small Cell Lung Cancer (BLOSSOM)

This is a very hard and depressing disease, but now with hope. EGFR-mutated NSCLS patients showed response to osimertinib in more than 50%, 15% complete response (CR), 15 months survival. This is promising, and maybe now we can study other TKIs in this mets.

Amivantamab plus Lazertinib in Previously Untreated EGFR-Mutated Advanced NSCLC

Another possible option for first line NSCLC EGFR mutated (non-exon 20) is Osimertinib (osi). Osi and chemotherapy had less brain metastases. And with Amivantamab and Lazertinib (EGFR inhibitor), the combination had better PFS and OS (HR0.8). Higher toxicity though with 10% discontinuation vs 3% for Osimertinib. This is interim analysis, toxicity was EGFR related mostly.