Real-world first-line treatment with pembrolizumab for non-small cell lung carcinoma with high PD-L1 expression: Updated analysis.

BACKGROUND: Selecting pembrolizumab monotherapy (MONO) or pembrolizumab plus platinum-based chemotherapy (COMB) for patients with nonsmall cell lung cancer (NSCLC) and high programmed death-ligand 1 (PD-L1) expression is an important issue in clinical practice. We previously conducted a retrospective multicenter observational study of patients with NSCLC and high PD-L1 expression who received MONO or COMB as a first-line treatment. Here, we report updated data and evaluate the long-term outcomes. METHODS: We performed a retrospective multicenter study of 298 patients with NSCLC and high PD-L1 expression who received MONO or COMB as first-line treatment between December 2018 and January 2020. We reviewed the medical records and assessed the clinical efficacy and toxicity using a prolonged data cutoff. RESULTS: In total, 164 (median age: 74 years) and 134 (median age: 68 years) patients received MONO and COMB, respectively; patients who received COMB were younger and had better performance statuses (0-1). At the prolonged data cutoff, the median follow-up was 20.2 (range: 0.1-41.4) months. The median progression-free survivals were 7.5 and 13.1 months, and overall survivals (OSs) were 17.2 and 33.7 months for MONO and COMB, respectively. Treatment discontinuation rates were 21.9% and 20.1% for the MONO and COMB, respectively. With prolonged follow-up, although COMB demonstrated an OS benefit and higher objective response rate than MONO, in the propensity score matching analysis COMB didn't demonstrate a significant benefit compared to the MONO. CONCLUSIONS: COMB may be effective as a first-line treatment for NSCLC with high PD-L1 expression in a selected subset of patients.

Real-World Data on Subsequent Therapy for First-Line Osimertinib-Induced Pneumonitis: Safety of EGFR-TKI Rechallenge (Osi-risk Study TORG-TG2101).

BACKGROUND: Although osimertinib is a promising therapeutic agent for advanced epidermal growth factor receptor (EGFR) mutation-positive lung cancer, the incidence of pneumonitis is particularly high among Japanese patients receiving the drug. Furthermore, the safety and efficacy of subsequent anticancer treatments, including EGFR-tyrosine kinase inhibitor (TKI) rechallenge, which are to be administered after pneumonitis recovery, remain unclear. OBJECTIVE: This study investigated the safety of EGFR-TKI rechallenge in patients who experienced first-line osimertinib-induced pneumonitis, with a primary focus on recurrent pneumonitis. PATIENTS AND METHODS: We retrospectively reviewed the data of patients with EGFR mutation-positive lung cancer who developed initial pneumonitis following first-line osimertinib treatment across 34 institutions in Japan between August 2018 and September 2020. RESULTS: Among the 124 patients included, 68 (54.8%) patients underwent EGFR-TKI rechallenge. The recurrence rate of pneumonitis following EGFR-TKI rechallenge was 27% (95% confidence interval [CI] 17-39) at 12 months. The cumulative incidence of recurrent pneumonitis was significantly higher in the osimertinib group than in the first- and second-generation EGFR-TKI (conventional EGFR-TKI) groups (hazard ratio [HR] 3.1; 95% CI 1.3-7.5; p = 0.013). Multivariate analysis revealed a significant association between EGFR-TKI type (osimertinib or conventional EGFR-TKI) and pneumonitis recurrence, regardless of severity or status of initial pneumonitis (HR 3.29; 95% CI 1.12-9.68; p = 0.03). CONCLUSIONS: Osimertinib rechallenge after initial pneumonitis was associated with significantly higher recurrence rates than conventional EGFR-TKI rechallenge.

Clinical outcomes in patients with non-small cell lung cancer harboring EGFR Exon20 in-frame insertions in the near-loop and far-loop: Results from LC-SCRUM-Asia.

OBJECTIVES: In this study, we explored the clinical outcomes of non-small cell lung cancer (NSCLC) patients with EGFR Exon20 in-frame insertions (Exon20ins), and the impact of the location of Exon20ins on these clinical outcomes. MATERIALS AND METHODS: The efficacies of current systemic therapies in NSCLC patients harboring Exon20ins were investigated using a large-scale clinico-genomic database of LC-SCRUM-Asia, and compared with that of amivantamab in the CHRYSALIS trial. RESULTS: Of the 11,397 patients enrolled in LC-SCRUM-Asia, Exon20ins were detected in 189 patients (1.7 %). Treatment with classical EGFR tyrosine-kinase inhibitors (classical TKIs) was associated with a significantly shorter progression-free survival (PFS) in NSCLC patients with Exon20ins as compared with Exon19 deletions and L858R. Post platinum-based chemotherapy, classical TKIs and immune checkpoint inhibitors (ICIs) were associated with a shorter PFS than with docetaxel in patients with Exon20ins (HR [95 % CI]; TKIs vs docetaxel, 2.16 [1.35-3.46]; ICIs vs docetaxel, 1.49 [1.21-1.84]). Patients treated with amivantamab in the CHRYSALIS trial showed a risk reduction in PFS and overall survival as compared with LC-SCRUM-Asia patients treated with docetaxel, classical TKIs, or ICIs. Among the 189 patients, Exon20ins were classified as near-loop or far-loop insertions in 115 (61 %) and 56 (30 %) patients, respectively. Treatment with osimertinib was associated with a longer PFS in patients with Exon20ins in near-loop as compared with far-loop (median, 5.6 vs. 2.0 months; HR [95 % CI], 0.22 [0.07-0.64]). CONCLUSIONS: After platinum-based chemotherapy, classical TKIs and ICIs are less effective in NSCLC patients with Exon20ins, and amivantamab may be a promising targeted therapy. There is a possibility that the location of Exon20ins has an impact on the efficacy of TKIs.

Durvalumab after chemoradiotherapy in non-small cell lung cancer with EGFR mutation: A real-world study (HOT2101).

Durvalumab has been administered to patients with unresectable stage III non-small cell lung cancer (NSCLC). However, it remains unclear whether durvalumab benefits these patients with epidermal growth factor receptor (EGFR) mutation. We conducted a retrospective, multicenter study of patients with EGFR mutation who received chemoradiotherapy (CRT) between June 2018 and March 2021. We assessed patient characteristics, efficacy of durvalumab, and durvalumab safety before and after targeted therapy. We collected data on a total of 673 patients, of whom 401 (59.6%) underwent EGFR mutation testing. Fifty-one patients were EGFR positive and 311 were EGFR negative. In the EGFR-positive group, there were higher proportions of females, never-smokers, and patients with adenocarcinoma histology. Of the 51 patients in the positive group and 311 in the negative group who received CRT, 45 (88.2%) and 247 (79.4%) received durvalumab, with median progression-free survival of 23.0 and 24.2 months in the positive and negative groups, respectively (hazard ratio 1.03; 95% confidence interval: 0.64-1.67). The main adverse event was pneumonitis (positive group: 62.2%; 4.4% grade 3; negative group: 62.3%; 6.9% grade 3). No treatment-related deaths were observed. Of the 45 patients in the positive group who received durvalumab, 14 (31.1%) received targeted therapy after durvalumab at the data cutoff. One patient discontinued targeted therapy after developing pneumonitis. In patients with unresectable stage III NSCLC with EGFR mutation, durvalumab after CRT is potentially safe and effective. This may be a suitable treatment sequence for these patients.