After TKI Resistance, a Chemo-Antiangiogenesis Combination May Benefit Some Patients With EGFR+ NSCLC

In patients with EGFR-positive non–small cell lung cancer who develop a T790M mutation after disease progression, chemo-antiangiogenesis may prove beneficial.

Chemo-antiangiogenesis combinations may be a preferred option for patients harboring a T790M mutation after disease progression following osimertinib treatment in patients with advanced non-small cell lung cancer, according to data published in the journal of Translational Lung Cancer Research.

Despite the high efficacy of epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) for the treatment of NSCLC, patients will inevitably develop drug resistance. Despite this, there is a lack of options past this in clinical practice.

In order to compare the efficacy of chemo-antiangiogensis or chemo-immunotherapy combinations after EGFR-TKI resistance, a 2-center retrospective study was conducted. Patients included in the retrospective were treated for EGFR-mutant NSCLC at Shanghai Pulmonary Hospital and Shanghai Chest Hospital between January 2015 and December 2020. Patients received either chemo-antiangiogensis or chemo-immunotherapy.

In total, 144 patients were identified and enrolled in the study. In order to be included, patients must have confirmed NSCLC, unresectable stage IIIB/IV disease, a confirmed EGFR mutation. Patients must also have one measurable lesion, an ECOG performance status of 0 to 2, and sufficient organ function. Patients with other drive mutations such as ALK/ROS1 rearrangements or have an ongoing response to EGFR TKIs were excluded.

In patients who received chemoimmunotherapy (n = 44), the median age was 63.5 (range, 19-76), 52.3% were male, and 79.5% were never smokers. Fifty percent of patients had 19Del and 45.5% had a L858R mutation. PD-L1 of ≥1% were seen in 6.8% of patients and 63.6% of patients had 0 to 1 metastatic site. Specific metastasis sites included brain (13.6%), liver (6.8%), and bone (38.6%). Over 50% of patients had received 2 lines of therapy.

In patients who received chemotherapy and antiangiogenesis (n = 100), the median age was 58.5 (range, 36-75), 55% were female, and 75% were never smokers. EGFR mutations include 19Del (55%), L858R (31%), rare mutations (11%), and unknown (3%). PD-L1 status of ≥1% were seen in 3% of patients. Forty-three percent of patients had 0 to 1 metastatic site. Metastases sites included brain (16%), liver (7%), and bone (40%). Fifty-two percent of patients had 2 prior lines of therapy.

In patients who received chemoimmunotherapy, the objective response rate to (ORR) to TKI treatment was 67.5%, with a disease control rate (DCR) of 95%. The partial response rate (PR) was 61.4%, the stable disease rate was 25%, and the progressive disease rate was 4.5%. The median duration of progression-free survival (PFS) with TKIs was 10.59 months. Sixteen percent of patients were T790M positive after TKI resistance. The ORR to subsequent therapies was 29.5% and the DCR was 88.6%. All responses were partial responses. Stable disease was seen in 59.1% of patients and progressive disease in 11.4% of patients. The median PFS of subsequent treatment was 7.59 months.

In patients who received chemotherapy and antiangiogenesis, the ORR to TKIs was 56.4% with a DCR of 92.3%. Partial responses were seen in 44% of patients, stable disease in 28% of patients, and progressive disease in 6% of patients. Twenty-two percent of patients were T790M positive after TKI resistance. The ORR for subsequent therapies in this population was 13% with a DCR of 93%. All responses were partial responses. Stable disease was seen in 80% of patients and progressive disease in 7% of patients.

“For patients who received chemo-immunotherapy combinations, the ORR and PFS were better in patients harboring EGFR L858R mutations than those harboring 19del mutations but showed no significant difference. However, patients who developed secondary T790M mutations after EGFR-TKI treatment were less likely to benefit from chemo-immunotherapy combinations.” wrote study authors.

REFERENCE:

Yu X, Li J, Zhao J, et al. Real-world outcomes of chemo-antiangiogenesis versus chemo-immunotherapy combinations in EGFR-mutant advanced non-small cell lung cancer patients after failure of EGFR-TKI therapy. Transl Lung Cancer Res. 2021; 10(9). doi: 10.21037/tlcr-21-681