nab-Paclitaxel-Based Therapy in Underserved Patient Populations: The ABOUND.70+ Study in Elderly Patients With Advanced NSCLC

Abstract

The phase 4 ABOUND.70+ trial assessed the safety and efficacy of nab-paclitaxel/carboplatin continuously or with a 1-week break between cycles in elderly patients with advanced non-small cell lung cancer (NSCLC). Patients ≥70 years with locally advanced/metastatic NSCLC were randomized 1:1 to first-line nab-paclitaxel days 1, 8, 15 plus carboplatin day 1 of a 21-day cycle (21d) or the same nab-paclitaxel/carboplatin regimen with a 1-week break between cycles (21d + break; 28d). The primary endpoint was the percentage of patients with grade ≥ 2 peripheral neuropathy (PN) or grade ≥ 3 myelosuppression. Other key endpoints included progression-free survival (PFS), overall survival (OS), and overall response rate (ORR). A total of 143 patients were randomized (71 to 21d, 72 to 21d + break). The percentage of patients with grade ≥ 2 PN or grade ≥ 3 myelosuppression was similar between the 21d and 21d + break arms (76.5 and 77.1%; P = 0.9258). Treatment exposure was lower in the 21d arm compared with the 21d + break arm. Median OS was 15.2 and 16.2 months [hazard ratio (HR) 0.72, 95% CI 0.44–1.19; P = 0.1966], median PFS was 3.6 and 7.0 months (HR 0.48, 95% CI 0.30–0.76; P < 0.0019), and ORR was 23.9 and 40.3% (risk ratio 1.68, 95% CI 1.02–2.78; P = 0.0376) in the 21d and 21d + break arms, respectively. In summary, the 1-week break between treatment cycles significantly improved PFS and ORR but did not significantly reduce the percentage of grade ≥ 2 PN or grade ≥ 3 myelosuppression. Overall, the findings support the results of prior subset analyses on the safety and efficacy of first-line nab-paclitaxel/carboplatin in elderly patients with advanced NSCLC.

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

“…5 The data from both the LCCC 1210 and ABOUND.70+ studies support this hypothesis, but only a randomized study of another taxane compared with nab-paclitaxel could truly confirm it. We did note that another study (the phase 4 ABOUND.70+ study 24 ) also was consistent, with a survival of 15.2 months to 16.2 months reported in older patients who were treated with carboplatin and nab-paclitaxel as first-line therapy.…”

“…The results of the current study support a broad body of data 2,3,24,25 demonstrating that chronologic age alone should not be used as a selection factor and that older patients can benefit from additional therapy after treatment with a platinum doublet. Although not definitive due to the nonrandomized nature of the data, the PFS and OS data from these 2 separate data sources further support the existing literature suggesting the promising efficacy of nab-paclitaxel in older patients with lung cancer.…”

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

“…Platinum doublet therapies have demonstrated an OS benefit compared with single-agent chemotherapy in fit elderly patients. 5,6,14 This benefit also was observed in patients receiving upfront immunotherapy alone or in combination with chemotherapy, thus representing a new standard of care for patients aged >65 years (KEYNOTE-24: OS HR, 0.45; IMPower-150: OS HR, 0.76; and KEYNOTE-189: OS HR, 0.63). 15,16,21 The articles by Youn et al 2 and Weiss et al 3 in this issue of Cancer have confirmed that there is no longer room for therapeutic nihilism in the management of older adults.…”

“…The median age of presentation of patients with mNSCLC is 71 years and therefore there is a critical need to clearly define a standard of care for the management of elderly patients. Platinum doublet therapies have demonstrated an OS benefit compared with single‐agent chemotherapy in fit elderly patients . This benefit also was observed in patients receiving upfront immunotherapy alone or in combination with chemotherapy, thus representing a new standard of care for patients aged >65 years (KEYNOTE‐24: OS HR, 0.45; IMPower‐150: OS HR, 0.76; and KEYNOTE‐189: OS HR, 0.63) .…”

“…This treatment benefit in elderly patients was thought to be related, in part, to a poorer tolerability of the every‐3‐week, solvent‐bound paclitaxel schedule. In a follow‐up, elderly‐specific trial (ABOUND 70+), patients were randomized to first‐line nab‐paclitaxel on days 1, 8, and 15 plus carboplatin on day 1 of a 21‐day cycle or to the same regimen with a 1‐week break between cycles . Although the OS was similar between the 2 arms, a significant improvement in progression‐free survival and the overall response rate was observed in patients treated with the 1‐week break, which may have been due to increased treatment exposure and the delayed onset of neuropathy.…”