Proffered Paper session I Proffered Paper session

LBA2 - Patient-reported outcomes (PROs) with durvalumab by PD-L1 expression in unresectable, stage III NSCLC (PACIFIC)

Presentation Number
LBA2
Lecture Time
17:30 - 17:45
Speakers
  • M. Garassino (Milan, Italy)
Location
Room C, Geneva Palexpo, Geneva, Switzerland
Date
Wed, 10.04.2019
Time
16:30 - 18:15
Authors
  • M. Garassino (Milan, Italy)
  • L. Paz-Ares (Madrid, Spain)
  • R. Hui (Westmead, NSW, Australia)
  • C. Faivre-Finn (Manchester, United Kingdom)
  • A. Spira (Fairfax, United States of America)
  • D. Planchard (Villejuif, France)
  • M. Ozguroglu (Istanbul, Turkey)
  • D. Daniel (Chattanooga, United States of America)
  • D. Vicente (Seville, Spain)
  • S. Murakami (Chou-ku, Tokyo, Japan)
  • A. Rydén (MÖLNDAL, Sweden)
  • Y. Zhang (Gaithersburg, MD, United States of America)
  • C. O'Brien (Macclesfield, United Kingdom)
  • P. Dennis (Gaithersburg, MD, United States of America)
  • S. Antonia (Tampa, FL, United States of America)

Abstract

Background

In the phase 3 PACIFIC study of unresectable, Stage III NSCLC pts without progression after platinum-based concurrent chemoradiotherapy (cCRT), the primary endpoints PFS and OS were significantly improved with durvalumab versus placebo with similar safety and no detrimental effect on PROs. We retrospectively investigated the impact of tumour PD-L1 expression on PROs to better understand the benefit/risk profile of durvalumab across all PD-L1 subgroups.

Background

In the ph 3 PACIFIC study of Stage III NSCLC pts without progression after cCRT, PFS and OS were significantly improved with durva vs. pbo, with no detrimental effect on PROs. We retrospectively investigated the impact of tumour PD-L1 expression on PROs.

Methods

After cCRT with ≥2 chemotherapy cycles, pts were randomised (2:1) to durvalumab 10 mg/kg or placebo IV q2w up to 12 months. If available, optional pre-cCRT tumour tissue was tested for PD-L1 tumour cell (TC) expression using the VENTANA SP263 immunohistochemistry assay and scored at pre-specified (25%) and post-hoc (1%) cutoffs. PROs were assessed using EORTC QLQ-C30 and -LC13 with changes from baseline (BL) analysed by a mixed model for repeated measures, hazard ratios (HRs) for time to deterioration (TTD) by a Cox proportional-hazards model, and odd ratios (ORs) for improvement rates by logistic regression.

Methods

After ≥2 cCRT cycles, pts were randomised (2:1) to durva 10 mg/kg or pbo IV q2w up to 12 mo. If available, optional pre-cCRT tumour tissue was tested for PD-L1 tumour cell (TC) expression using the VENTANA SP263 immunohistochemistry assay and scored at pre-specified (25% or unknown) and post-hoc (1%) cutoffs. PROs were assessed using EORTC QLQ-C30 and -LC13 with changes from BL analysed by a mixed model for repeated measures, HRs for time to deterioration (TTD) by a stratified Cox proportional-hazards model, and ORs for improvement rates by logistic regression.

Results

Of 713 pts, 63% had known PD-L1 status. Similar to the intent-to-treat (ITT) population, most PROs remained stable over time from BL across the PD-L1 subgroups (TC ≥25%, <25%, ≥1%, <1%, or unknown), with no clinically meaningful (CM) differences (≥10 points) for durvalumab compared to placebo. However, similar to the ITT population, CM improvements (decreases ≥10 points) from BL to Week 48 were observed for dysphagia and alopecia across most PD-L1 subgroups for both durvalumab (mean changes 8.1 [not CM]−20.9 and 15.5 − 26.9, respectively) and placebo (mean changes 10.4 − 19.4 and 15.8 − 31.3). Pre-specified and post hoc TTD analyses of PROs by PD-L1 subgroup were generally similar to those of the ITT population, with overlapping HR and 95% CIs. Similarly, PRO improvement rates by PD-L1 subgroup were generally similar to those of the ITT population, with overlapping OR and 95% CIs.

Results

Of 713 pts, 63% had known PD-L1 status. Compliance was high (>80% at Wk 48) across all five PD-L1 subgroups (TC ≥25%, <25%, ≥1%, <1%, and unknown). Most PROs remained stable; however, similar to the ITT population, clinically relevant improvements from BL to Wk 48 were observed for dysphagia and alopecia across most subgroups (4/5 and 5/5, respectively) for durva (mean changes 10.1−20.9 and 15.5−26.9) and all for pbo (10.4−19.4 and 15.8−31.3); plus improvements with pbo for TC ≥25% (12.5 for chest pain and constipation) and TC <25% (10.0 for appetite loss and arm/shoulder pain). Across most subgroups, there were no TTD differences, except those favouring durva: for TC ≥25%, chest pain (HR=0.57), physical functioning (0.60), emotional functioning (0.47), pain (0.56), and haemoptysis (0.42); and, similar to ITT, for TC ≥25%, <25%, ≥1% and <1%, ‘other pain’ (0.60, 0.57, 0.67 and 0.39, respectively). Improvement rates were also similar, except as follows, favouring durva: for TC ≥25%, role functioning (OR=2.84) and, similar to ITT, appetite loss (4.33); for TC ≥1%, diarrhoea (4.50) and haemoptysis (19.34); and, for TC<1%, ‘other pain’ (7.25); for TC<25%, the rate favoured pbo for cough (0.51).

Conclusions

There were no CM differences in PROs between treatment arms across various PD-L1 subgroups. Results were generally consistent with those in the ITT population, suggesting that PD-L1 expression did not influence PROs in this study.

Conclusions

Similar to the ITT population, there were minimal between-Tx differences in PROs based on PD-L1 expression, supporting use of the PACIFIC regimen (durvalumab after cCRT) in all comers.

Clinical trial identification

NCT02125461

Editorial acknowledgement

Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Hashem Dbouk, PhD, of Cirrus Communications, an Ashfield company, and was funded by AstraZeneca.

Editorial acknowledgement

Medical writing support, which was in accordance with Good Publication Practice (GPP3) guidelines, was provided by Andrew Gannon of Cirrus Communications, an Ashfield company, and funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca.

Funding

AstraZeneca.

Disclosure

M.C. Garassino: Personal fees: AstraZeneca, Roche, BMS, MSD. L. Paz-Ares: Advisory fees: BMS, Lilly, MSD, AstraZeneca, Roche, Pfizer, Novartis, Incyte, Merck, Boehringer Ingelheim, outside the conduct of the study. C. Faivre-Finn: Research funding: AstraZeneca, MSD, outside the conduct of the study. A. Spira: Consultant fees, institutional research support: AstraZeneca, outside the conduct of the study. D. Planchard: Personal fees: AstraZeneca, Boehringer Ingelheim, BMS, MSD, Pfizer, Novartis, Roche, Celgene, outside the conduct of the study. M. Ozguroglu: Consultant fees: Astellas; Honoraria: Janssen, outside the conduct of the study. A. Rydén, P.A. Dennis: Employment, stock: AstraZeneca. Y. Zhang, C. O’Brien: Employment, stock: AstraZeneca, outside the conduct of the study. All other authors have declared no conflicts of interest.

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Proffered Paper session I Proffered Paper session

Invited Discussant 83O, LBA2 and LBA4

Lecture Time
18:00 - 18:15
Speakers
  • F. Barlesi (Marseille, CEDEX 20, France)
Location
Room C, Geneva Palexpo, Geneva, Switzerland
Date
Wed, 10.04.2019
Time
16:30 - 18:15
Authors
  • F. Barlesi (Marseille, CEDEX 20, France)