Efficacy and Safety of Low-Dose Nab-Paclitaxel Plus Tislelizumab in Elderly Patients With Previously Treated Metastatic Non-Small Cell Lung Cancer

Abstract

The combination of immunotherapy and chemotherapy has a synergic effect in non-small cell lung cancer (NSCLC). However, the elderly are often excluded from clinical trails due to their poor health status and more comorbidities. We sought to assess the efficacy and safety of low-dose nanoparticle albumin-bound paclitaxel (nab-paclitaxel) plus tislelizumab (an anti-PD-1 antibody) in elderly patients with advanced NSCLC. In this phase 2 clinical trail, eligible patients were those aged ≥65 years with metastatic NSCLC who had disease progression after treatment with ≥1 line of chemotherapy or targeted therapy. Patients with epidermal growth factor receptor (EGFR) or anaplastic lymphoma kinase (ALK) variations were eligible if they demonstrated disease progression after treatment with ≥1 corresponding inhibitor. Primary endpoints were progression-free survival and safety/tolerability. Secondary endpoints included objective response rate and overall survival. Among 29 patients enrolled from May 2019 through August 2020, 21 (72.4%) had adenocarcinoma, 17 (58.6%) had a performance status of 2, 8 (27.6%) had asymptomatic brain metastases, and 13 (44.8%) had EGFR/ALK variations. As of the data cutoff point on April 1, 2021, median progression-free survival and overall survival were 9.5 months and 16.5 months, respectively. Ten patients achieved a partial response (objective response rate of 34.5%). Seventeen (58.6%) patients had ≥1 treatment-related adverse event, with grade 3 events seen in 3 patients (10.3%). The most common adverse events were fatigue (20.7%), fever (17.2%), abnormal liver function (17.2%), and rash (17.2%). These results suggest that low-dose nab-paclitaxel plus tislelizumab is well tolerated and effective in elderly patients with advanced NSCLC, including those with EGFR/ALK variations.

Efficacy and safety of reduced‐dose chemotherapy plus immunotherapy in patients with lung squamous cell carcinoma: A real‐world observational study

“…These results suggest that reduced‐dose chemotherapy, plus immunotherapy benefits elderly and frail patients. Similarly, the promising efficacy of reduced‐dose nab‐paclitaxel plus tislelizumab in elderly patients was corroborated in a phase II Chinese clinical trial 17 . The study included patients with LUAD and LUSC; the ORR and PFS were 34.5% and 9.5 months (95% CI, 5.8–13.2), respectively.…”

“…Recent literature indicates that reduced‐dose chemotherapy is as effective as full‐dose chemotherapy in elderly patients 17,19 . In addition, some studies have demonstrated that reduced‐dose chemotherapy can enhance antigen release, remodel the active LUSC immune microenvironment, and increase synergistic effects 20–22 .…”

“…Elderly patients and those with a poor performance status (PS) 15,16 may struggle to tolerate full‐dose chemotherapy, especially when combined with PD‐1/PD‐L1 inhibitors, because they are more likely to have complications, frailty, and weaker bone marrow function. Consequently, this patient population continuously remains understudied 17 . Therefore, individualized and precise treatments should be considered for these populations.…”

“…Consequently, this patient population continuously remains understudied. 17 Therefore, individualized and precise treatments should be considered for these populations.…”

“…Recent literature indicates that reduced‐dose chemotherapy is as effective as full‐dose chemotherapy in elderly patients. 17 , 19 In addition, some studies have demonstrated that reduced‐dose chemotherapy can enhance antigen release, remodel the active LUSC immune microenvironment, and increase synergistic effects. 20 , 21 , 22 Consequently, we hypothesized that combining reduced‐dose chemotherapy with immunotherapy might benefit patients with LUSC while reducing toxicities.…”