Nab‐paclitaxel in older patients with non–small cell lung cancer who have developed disease progression after platinum‐based doublet chemotherapy

Abstract

Background The selection of later‐line treatment for older patients with AJCC (version 7) stage IV non–small cell lung cancer (NSCLC) remains controversial. Nanoparticle albumin–bound (nab)‐paclitaxel is approved with carboplatin for the first‐line treatment of patients with NSCLC and subgroup analysis of phase 3 data has suggested superior survival in older patients. Methods The authors conducted a phase 2 study of nab‐paclitaxel in 42 patients aged ≥70 years who had been treated previously with a platinum doublet regimen; patients also could have received a PD‐1 inhibitor. The primary endpoint of the current study was grade 3 to 5 toxicity (according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]). In addition to response rate, progression‐free survival (PFS), and overall survival (OS), geriatric assessments also were performed before and during treatment, associations between baseline sarcopenia and outcomes were explored, and changes in T lymphocyte p16 before and during treatment were measured. The authors also performed a retrospective subgroup analysis of 19 older patients who were treated with nab‐paclitaxel as part of a larger, randomized, phase 2 study; data were not combined. Results The rate of grade 3 to 5 toxicities was 33.7%. The most common grade 3 to 5 toxicities were decreased white blood cell count (11.9%), neutropenia (9.5%), and fatigue (11.9%). The response rate was 34.2% (2.6% complete response rate and 31.6% partial response rate). The median PFS was 5.2 months and the median OS was 9.3 months. Adverse prognostic factors were common: 42% of patients were frail and 39% of patients were prefrail, whereas 21% had an Eastern Cooperative Oncology Group performance status of 2 and 27% were sarcopenic. Only frailty was found to be predictive of inferior survival. A subgroup analysis of 19 older patients treated with nab‐paclitaxel alone in a prior trial demonstrated a response rate of 15.8%, a PFS of 4.2 months, and an OS of 13.6 months. Conclusions Fit and prefrail older patients with stage IV NSCLC should be considered for treatment with nab‐paclitaxel after disease progression with doublet chemotherapy.

Systemic therapy for elderly patients with non–small cell lung cancer: Where do we stand in 2019?

“…Together, these results suggest that the nab‐paclitaxel combination might be the preferred approach in elderly patients. The current trial from Weiss et al built on these observations and extended the applicability of previous results to the use of single‐agent nab‐paclitaxel in the second‐line setting.…”

“…In this issue of Cancer , Youn et al and Weiss et al have provided evidence regarding the outcomes of elderly patients with metastatic NSCLC (mNSCLC) who were treated with immunotherapy in a real‐world setting and clinical trial experience using single‐agent nab‐paclitaxel chemotherapy, respectively. Although historically single‐agent chemotherapy has been the preferred modality for therapy in elderly patients, clinical trials evaluating carboplatin‐based doublet therapy in treatment‐naive patients have demonstrated superiority to standard single agents, establishing these regimens as the current standard of care for fit elderly patients .…”

“…Thus, there is a major limitation in generalizing the conclusions of such trials, highlighting the need for prospective, elderly‐specific clinical trials. Weiss et al reported the results of one such elderly‐specific clinical trial in patients aged >70 years evaluating the use of single‐agent nab‐paclitaxel in the second‐line setting. A total of 42 patients were enrolled, 42% of whom were classified as “frail.” The study by Weiss et al allowed patients with an ECOG PS of 2 to participate, who constituted approximately 21% of the study population.…”

“…Weiss et al reported the results of one such elderly‐specific clinical trial in patients aged >70 years evaluating the use of single‐agent nab‐paclitaxel in the second‐line setting. A total of 42 patients were enrolled, 42% of whom were classified as “frail.” The study by Weiss et al allowed patients with an ECOG PS of 2 to participate, who constituted approximately 21% of the study population. Approximately one‐third of the patients experienced toxicity of ≥grade 4 (according to the National Cancer Institute Common Terminology Criteria for Adverse Events [version 4.0]), and the median OS was 9.3 months.…”

PD-1/PD-L1 Based Combinational Cancer Therapy: Icing on the Cake

“…Despite some disadvantages, checkpoint inhibitors possess a great prospect. The recent findings suggest that PD-1/PD-L1 inhibitors may be combined with other immunotherapies or traditional treatments to enhance efficacy relative to that using PD-1/PD-L1 therapy alone, which always exhibit higher response rates, reducing adverse reaction and drug resistance (Li J. et al, 2019;Zhang et al, 2019;Li et al, 2020;Shao et al, 2020;Sonpavde et al, 2020;Wan et al, 2020;Weiss et al, 2020;Zhang et al, 2020). Some researchers have shown the prospects of anti-PD-L1 and anti-CTLA-4 combination therapy, which revealed PD-L1:CD80 (CTLA-4 ligand) cis-heterodimerization inhibited both PD-L1: PD-1 and CD80:CTLA-4 interactions.…”