2559 - Impact of adjuvant treatment with nab-paclitaxel and gemcitabine (nab-P+GEM) vs gemcitabine alone (GEM) on health-related quality of life (QoL) in patients (pts) with surgically resected pancreatic adenocarcinoma (PA) in the Adjuvant Pancreatic Adenocarcinoma Clinical Trial (APACT)

Background

The APACT trial compared disease-free survival in pts with surgically resected PA randomized to nab-P+GEM or GEM as adjuvant regimens. We compared the QoL impact of both regimens in the biggest cohort of pts (n = 379/arm) in which QoL was studied in this setting.

Methods

The European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30 and pancreatic cancer module (PAN26) scores were assessed in 12-week intervals at screening (BL), middle and end of treatment (EOT), and up to 2.5 years of follow-up (FU). A mixed model for repeated measures analysis adjusting for BL score was conducted to predict scores by arm at each visit. Time until definite deterioration (TUDD) and improvement (TUDI) were compared between arms, separately during treatment and FU, using a minimal important difference (MID) threshold of 10-points for all QLQ-C30 scales and scale-specific thresholds for PAN26.

Results

The proportion of pts with QoL data at EOT, year 1, and year 3 were 88%, 51%, and 17%, with similar attrition in both arms. The predicted differences between arms for global health (GH) and all but 1 subscale of the QLQ C-30 never reached the predefined MID threshold (Table). nab-P+GEM pts had meaningfully worse predicted scores than GEM pts on 6 of 17 PAN26 scales during treatment, but these differences persisted for only 2 scales at 2 FU visits. For TUDD and TUDI, nab-P+GEM pts deteriorated faster during treatment, but TUDD did not differ for domain-specific or GH scales between arms at FU, during which nab-P+GEM pts improved faster on some scales, including GH.Table:

684P QLQ-C30 and PAN26 scales assessed through MMRM, TUDD, and TUDI analyses demonstrating clinically and statistically significant differences between nab-P+GEM vs GEM

AE, treatment related adverse event; AL, appetite loss; BI, body image; DM, dryness of mouth; DS, digestive symptoms; DY, dyspnea; EOT, end of treatment; FA, fatigue; FH, worried about future health; GH, global health; IN, indigestion; LA, limited activities; MMRM, mixed model for repeated measures; MOT, middle of treatment; PA, pain; PF, physical function; PP, Pancreatic Pain; RF, role function; SF, social function; SX, sexual dysfunction; TA, taste change; TUDD, time until definite deterioration; TUDI, time until definite improvement; WE, weakness in arms and legs. w36 or w48 = clinically and statistically significantly up to week 36 or week 48. a During treatment = MOT and EOT. b Follow-up = EOT to week 156. c Mean predicted scores for nab-P+GEM vs GEM for visits until clinical and statistical differences persisted. d Hazard ratio not including 1.00. e Higher score indicates better QoL. f Higher score indicates worse QoL. g Hazard Ratio >1 indicate higher rate of deterioration and <1 indicate lower rate of deterioration in nab-P+GEM h Hazard Ratio >1 indicate higher rate of improvement and <1 indicate lower rate of improvement in nab-P+GEM

Conclusions

As expected, nab-P+GEM is associated with temporary reductions in some QoL dimensions vs GEM alone. Over the long term, QoL was not compromised by adding nab-P to GEM as adjuvant therapy for surviving and reporting pts.

Clinical trial identification

ABI-007-PANC-003.

Editorial acknowledgement

Pharmerit International.

Legal entity responsible for the study

The authors.

Funding

Celgene Corporation.

Disclosure

H. Riess: Advisory / Consultancy: Bayer, Boehringer-Ingelheim, Bristol-Myers-Squibb, Celgene, Daiichi-Sankyo, Johnson & Johnson, Pfizer; Speaker Bureau / Expert testimony: Bayer, Boehringer-Ingelheim, Bristol-Myers-Squibb, Celgene, Daiichi-Sankyo, Leo-Pharma, Pfizer; Research grant / Funding (institution): Bayer, Celgene, Leo Pharma. J. Braverman: Full / Part-time employment: Celgene Corporation. M. Reni: Non-remunerated activity/ies, Personal Fees: Celgene, Baxalta, Shire, eli-lilly, Pfizer, Novocure, Novartis, AstraZeneca. D. Oh: Advisory / Consultancy: Genentech/Roche, AstraZeneca, Novartis, Merck Serono, Bayer, Taiho, ASLAN, Halozyme, Zymeworks; Research grant / Funding (institution): AstraZeneca, Novartis, Array, Eli Lilly. T. Macarulla Mercade: Honoraria (self): Roche, Sanofi, Tesaro, Shire, Genzyme; Advisory / Consultancy: Baxalta, Celgene, H3B, QED, Shire; Speaker Bureau / Expert testimony: Celgene, Sanofi/Aventis, Shire; Research grant / Funding (self): Agios, Aslan, AstraZeneca, Bayer, Celgene, Genetech, Hallozyme, Immunomedics, Lilly, Merimarck, Millennium, Novartis, Novocure, Pfizer, Pharmacyclics, Roche; Travel / Accommodation / Expenses: Bayer, H3B, Merck, Sanofi. A. Shah: Full / Part-time employment: Pharmerit International; Non-remunerated activity/ies, Financial Support: Bayer, Celgene, Pfizer, Insmed. N. Joshi: Full / Part-time employment: Pharmerit International; Advisory / Consultancy, Consulting Fee: Celgene Corporation. M. Botterman: Honoraria (institution): Celgene, Bayer, Daiichi, BMS. E. Mantovani: Shareholder / Stockholder / Stock options, Full / Part-time employment: Celgene Corporation. B. Lu: Shareholder / Stockholder / Stock options, Full / Part-time employment: Celgene Corporation. M.A. Tempero: Advisory / Consultancy: AbbVie, Advance Medical, BioPharm Communications, BMS, Celgene, Eisai, Ignyta, Pharmacyslics, Pharmcyte Biotech, Tocagen; Advisory / Consultancy, Advisory Board: AstraZeneca, CPRIT, Immunovia; Research grant / Funding (self), Research Contract: Halozyme. All other authors have declared no conflicts of interest.