Nanoparticle Albumin-bound Paclitaxel Plus Carboplatin Induction Followed by Nanoparticle Albumin-bound Paclitaxel Maintenance in Squamous Non-Small-cell Lung Cancer (ABOUND.sqm): A Phase III Randomized Clinical Trial.
Spigel, David R. 1, *; Jotte, Robert M. 2; Aix, Santiago Ponce 3; Gressot, Laurent 4; Morgensztern, Daniel 5; McCleod, Michael 6; Socinski, Mark A. 7; Daniel, Davey 8; Juan-Vidal, Oscar 9; Mileham, Kathryn F. 10; West, Howard 11; Page, Ray 12; Reinmuth, Niels 13; Knoble, Jeanna 14; Chen, Tianlei 15; Bhore, Rafia 15; Wolfsteiner, Marianne 16; Ong, Teng Jin 15; Gridelli, Cesare 17; Thomas, Michael 18; on behalf of the ABOUND.sqm Investigators
[Article]
Clinical Lung Cancer.
22(1):6-15,15e1-15e4, January 2021.
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Background: We evaluated maintenance nanoparticle albumin-bound (nab) paclitaxel in the treatment of advanced squamous non-small-cell lung cancer.
Patients and Methods: Patients with treatment-naive squamous non-small-cell lung cancer received four 21-day cycles of nab-paclitaxel 100 mg/m2 on days 1, 8, 15 plus carboplatin area under the curve 6 on day 1 as induction therapy. Patients without disease progression after induction were randomized 2:1 to maintenance nab-paclitaxel 100 mg/m2 (days 1 and 8 every 21 days) plus best supportive care (BSC) or BSC alone. The primary endpoint was progression-free survival (PFS). Secondary endpoints included safety and overall survival (OS).
Results: Overall, 420 patients had received induction therapy; 202 (nab-paclitaxel plus BSC, 136; BSC, 66) had received maintenance therapy. Enrollment was discontinued after a preplanned interim futility analysis (patients could remain in the study at the investigator's discretion). The median PFS was 3.12 months for nab-paclitaxel plus BSC and 2.60 months for BSC; the difference was not statistically significant (hazard ratio [HR], 0.85; 95% confidence interval [CI], 0.61-1.19; P = .36). The median OS (median follow-up, 24.2 months) was 17.18 months for nab-paclitaxel plus BSC and 12.16 months for BSC (HR, 0.70; 95% CI, 0.48-1.02; nominal P = .07). An updated analysis (median follow-up, 28.4 months) revealed a median OS of 17.61 months for nab-paclitaxel plus BSC and 12.16 months for BSC (HR, 0.68; 95% CI, 0.47-0.98; nominal P = .037). The most frequent grade 3 and 4 treatment-emergent adverse events for the entire study were neutropenia (53.1% [nab-paclitaxel plus BSC] vs. 50.0% [BSC]) and anemia (33.1% [nab-paclitaxel plus BSC] vs. 32.3% [BSC]). Only peripheral neuropathy had occurred in >= 5% of patients during maintenance therapy (13.1%; nab-paclitaxel plus BSC).
Conclusions: The results of the ABOUND.sqm did not meet the primary endpoint of PFS. An updated OS analysis revealed a trend favoring nab-paclitaxel plus BSC.
Micro-Abstract: Prospective randomized studies of maintenance therapy for patients with squamous non-small-cell lung cancer are lacking. In the present study, patients without disease progression after induction treatment were randomized 2:1 to maintenance nanoparticle albumin-bound paclitaxel plus best supportive care or best supportive care alone. The primary endpoint (progression-free survival) was not met. Given the current treatment paradigm, these findings can be expected to minimally affect treatment practice.
(C) 2021Elsevier, Inc.