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Proffered Paper 1 – Non-metastatic NSCLC and other thoracic malignancies (SCLC)

3837 - PD-L1 expression, patterns of progression and patient-reported outcomes (PROs) with durvalumab plus platinum-etoposide in ES-SCLC: Results from CASPIAN

Date

28 Sep 2019

Session

Proffered Paper 1 – Non-metastatic NSCLC and other thoracic malignancies (SCLC)

Presenters

Luis Paz-Ares

Citation

Annals of Oncology (2019) 30 (suppl_5): v851-v934. 10.1093/annonc/mdz394

Authors

L. Paz-Ares1, J.W. Goldman2, M.C. Garassino3, M. Dvorkin4, D. Trukhin5, G. Statsenko6, K. Hotta7, J.H. Ji8, M.J. Hochmair9, O. Voitko10, L. Havel11, A. Poltoratskiy12, G. Losonczy13, N. Reinmuth14, Y. Shrestha15, N. Patel16, H. Mann17, H. Jiang18, M. Özgüroğlu19, Y. Chen20

Author affiliations

  • 1 Medical Oncology, University Hospital 12 De Octubre, 28041 - Madrid/ES
  • 2 Division Of Medicine, David Geffen School of Medicine at UCLA, 90404 - Los Angeles/US
  • 3 Thoracic Unit, Fondazione IRCCS - Istituto Nazionale dei Tumori, 20133 - Milan/IT
  • 4 Department Of Oncology, BHI of Omsk Region Clinical Oncology Dispensary, Omsk/RU
  • 5 Oncology Department, National Medical University, Odessa/UA
  • 6 Department Of Medical Oncology, Omsk Regional Cancer Center, Omsk/RU
  • 7 Center Of Innovative Clinical Medicine, Okayama University Hospital, 700-0005 - Okayama/JP
  • 8 Department Of Internal Medicine, Samsung Changwon Hospital, Sungkyunkwan University School of Medicine, Changwon/KR
  • 9 Department Of Respiratory And Critical Care Medicine, Karl Landsteiner Institute of Lung Research and Pulmonary Oncology, Krankenhaus Nord, 1140 - Vienna/AT
  • 10 Department Of Chemotherapy, Kyiv City Clinical Oncology Center, Kiev/UA
  • 11 First Faculty Of Medicine, Thomayer Hospital, Charles University, 180 00 - Prague/CZ
  • 12 Department Of Preclinical And Clinical Trials, Petrov Research Institute of Oncology, St Petersburg/RU
  • 13 Faculty Of Medicine, Semmelweis University, 1085 - Budapest/HU
  • 14 Thoracic Oncology, Asklepios Lung Clinic, Munich-Gauting/DE
  • 15 Translational Medicine, AstraZeneca, 20878 - Gaithersburg/US
  • 16 Patient Reported Outcomes, AstraZeneca, Gaithersburg/US
  • 17 Research And Development, AstraZeneca, Cambridge/GB
  • 18 Global Medicines Development, AstraZeneca, Gaithersburg/US
  • 19 Department Of Internal Medicine, Istanbul University−Cerrahpaşa, Cerrahpaşa School of Medicine, Istanbul/TR
  • 20 Medical Oncology, Cancer & Hematology Centers of Western Michigan, Grand Rapids/US
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Abstract 3837

Background

In the phase III CASPIAN trial, durvalumab (D) in combination with etoposide plus either cisplatin or carboplatin (EP) significantly improved the primary endpoint of OS vs EP alone in pts with extensive-stage small-cell lung cancer (ES-SCLC). Here we describe clinically relevant analyses for D + EP vs EP based on PD-L1 expression, progression patterns and PROs.

Methods

Tx-naive ES-SCLC (WHO PS 0/1) pts received 4 cycles of EP plus D q3w followed by maintenance D q4w or up to 6 cycles of EP q3w + prophylactic cranial irradiation (PCI; investigator’s discretion). PD-L1 expression in optional archival tissue was tested by VENTANA PD-L1 (SP263) immunohistochemistry assay. PROs were assessed using EORTC QLQ-C30/LC13 with changes from baseline analysed by time to deterioration (TTD) per Cox proportional hazards.

Results

As of 11 March 2019, 265 and 266 pts had received D + EP and EP, respectively. Of 277 with evaluable samples (D + EP, 151; EP, 126), PD-L1 expression was low (5% and 22% of pts with expression ≥1% in tumour (TC) and immune cells (IC), respectively). Evaluating PD-L1 expression as a continuous variable in either TC or IC indicated no significant impact of PD-L1 on Tx effect between arms for OS (P = 0.54 and 0.23, respectively); nor for PFS and ORR. Progression patterns were similar, although fewer pts developed new lesions at first progression with D + EP vs EP (41.4% vs 47.2%), including lung lesions (8.6% vs 15.2%). The incidence of new brain/CNS metastases was similar between arms (11.6% vs 11.5%), despite PCI allowance in the control arm only. Baseline PRO scores were comparable across all symptoms and functional domains. TTD was longer across all PROs for D + EP (favourable HRs, many with upper 95% CIs <1; Table 1).Table: LBA89

Time to deterioration (TTD) in PROs for D + EP vs. EP*

PRO variableHR for TTD (95% CI)Median, months
Global health status/QoL (C30)0.81 (0.626, 1.054)8.4 vs. 7.2
P = 0.1166
Functioning (C30)
Physical0.75 (0.581, 0.970)8.5 vs. 6.5
P = 0.0276
Cognitive0.61 (0.472, 0.776)8.4 vs. 6.0
P < 0.0001
Emotional0.61 (0.464, 0.800)12.9 vs. 7.3
P = 0.0003
Role0.71 (0.550, 0.904)7.4 vs. 5.9
P = 0.0059
Social0.70 (0.549, 0.897)7.6 vs. 6.2
P = 0.0048
Key symptoms
Appetite loss (C30)0.70 (0.542, 0.899)8.3 vs. 6.6
P = 0.0054
Fatigue (C30)0.82 (0.653, 1.027)5.5 vs. 4.3
P = 0.0835
Cough (LC13)0.78 (0.600, 1.026)9.3 vs. 7.7
P = 0.0747
Dyspnoea (LC13)0.79 (0.625, 1.006)6.5 vs. 5.5
P = 0.0578
Chest pain (LC13)0.76 (0.575, 0.996)10.6 vs. 7.8
P = 0.0464
*

261 D + EP pts and 260 EP pts evaluable for PRO.

PRO endpoints were not adjusted for multiplicity; hence, reported P values are nominal.

Calculated by Kaplan-Meier method.

HR, hazard ratio.

Conclusions

D + EP provided significant OS benefit over EP alone, while preserving QoL and increasing the time to worsening of symptoms and functioning. PD-L1 expression was low and did not appear to be a predictive biomarker for D + EP.

Clinical trial identification

NCT03043872 (release date: February 6, 2017).

Editorial acknowledgement

Medical writing support was provided by Andrew Gannon, MA, MS, of Cirrus Communications (New York, NY), an Ashfield company, and funded by AstraZeneca.

Legal entity responsible for the study

AstraZeneca PLC.

Funding

AstraZeneca PLC.

Disclosure

L. Paz-Ares: Leadership role: Genomica; Honoraria (self), Travel / Accommodation / Expenses, Spouse / Financial dependant: Roche; Honoraria (self), Travel / Accommodation / Expenses: AstraZeneca; Honoraria (self), Travel / Accommodation / Expenses: MSD; Honoraria (self), Travel / Accommodation / Expenses: Bristol-Myers Squibb; Honoraria (self), Travel / Accommodation / Expenses: Lilly; Honoraria (self), Travel / Accommodation / Expenses, Spouse / Financial dependant: Pfizer; Honoraria (self), Spouse / Financial dependant: Novartis; Spouse / Financial dependant: Ipsen; Spouse / Financial dependant: SERVIER; Spouse / Financial dependant: Sanofi; Honoraria (self), Spouse / Financial dependant: Amgen; Honoraria (self), Spouse / Financial dependant: Merck; Honoraria (self): Boehringer Ingelheim; Honoraria (self): PharmaMar; Honoraria (self): Celgene; Honoraria (self): Sysmex; Honoraria (self): Incyte. J.W. Goldman: Advisory / Consultancy, Research grant / Funding (institution): AstraZeneca; Advisory / Consultancy, Research grant / Funding (institution): Genentech; Advisory / Consultancy, Research grant / Funding (institution): Lilly; Speaker Bureau / Expert testimony: Merck; Research grant / Funding (institution): Bristol-Myers Squibb; Research grant / Funding (institution): Array BioPharma; Research grant / Funding (institution): Celgene; Research grant / Funding (institution): AbbVie. M.C. Garassino: Honoraria (self): MSD; Honoraria (self): BMS; Honoraria (self): AstraZeneca; Honoraria (self): Roche. K. Hotta: Honoraria (self), Research grant / Funding (institution): AstraZeneca; Honoraria (self), Research grant / Funding (institution): Lilly; Honoraria (self): MSD; Honoraria (self), Research grant / Funding (institution): BMS; Honoraria (self): Ono; Honoraria (self): Nipponkayaku; Honoraria (self): Taiho; Honoraria (self): Boehringer Ingelheim; Honoraria (self): Chugai. N. Reinmuth: Honoraria (self), Non-remunerated activity/ies: AstraZeneca; Honoraria (self), Non-remunerated activity/ies: Böhrigner Ingelheim; Non-remunerated activity/ies: AbbVie; Honoraria (self), Non-remunerated activity/ies: Hoffmann-La Roche; Honoraria (self): MSD SHARP & DOHME GMBH; Honoraria (self): Takeda; Honoraria (self), Non-remunerated activity/ies: Bristol-Myers Squibb; Honoraria (self), Non-remunerated activity/ies: Pfizer. Y. Shrestha: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. N. Patel: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. H. Mann: Full / Part-time employment: AstraZeneca. H. Jiang: Shareholder / Stockholder / Stock options, Full / Part-time employment: AstraZeneca. M. Özgüroğlu: Honoraria (self), Honoraria (institution), Advisory / Consultancy, Travel / Accommodation / Expenses: Janssen; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Sanofi; Honoraria (self), Honoraria (institution), Advisory / Consultancy: Astellas; Travel / Accommodation / Expenses: BMS. Y. Chen: Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): AstraZeneca; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Genetech; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony, Research grant / Funding (institution): Brystol-Myers Squibb; Honoraria (self), Speaker Bureau / Expert testimony: Merck; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Novartis; Honoraria (self), Advisory / Consultancy, Speaker Bureau / Expert testimony: Takeda; Honoraria (self), Speaker Bureau / Expert testimony: Eli-Lilly ; Honoraria (self), Speaker Bureau / Expert testimony: Guardant Health; Honoraria (self), Advisory / Consultancy: Pfizer; Honoraria (self), Advisory / Consultancy: Array Biopharma; Research grant / Funding (institution): ISPEN; Research grant / Funding (institution): Roche. All other authors have declared no conflicts of interest.

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