ESMO 2018 Congress | OncologyPRO

Abstract 2680

Background

CIT is associated with delayed onset of clinical effect and long-term (LT) survival, making traditional proportional hazards models less applicable. This study used a novel method, Bayesian fractional polynomial (FP) network meta-analysis (NMA) of time-to-event data, to address challenges in evaluating overall survival (OS) and switching with CIT.

Methods

A systematic literature review identified randomized, controlled, Phase II-IV trials of US- or EU-approved 2L+ treatments for advanced/metastatic NSCLC that enrolled ≥ 10 adult patients (pts) per treatment arm. An FP-NMA was used to estimate time-to-event outcomes: OS (5-y horizon) and progression-free survival (PFS; 2.5-y horizon). Expected survival time reflected the area under the curve over the time horizon. Adjusted analyses accounted for treatment switching. Expected OS times were ranked by median ranking with 95% credible intervals and by surface under the cumulative ranking curve (SUCRA).

Results

Of 25,115 screened publications, 35 studies of chemotherapy (chemo), PD-(L)1 inhibitors, targeted and other non-chemo agents, and placebo were included in the FP-NMA. In this model, all CIT PD-(L)1 inhibitors (nivolumab [nivo], atezolizumab [atezo] and pembrolizumab [pembro] in rank order) had similar estimated 5-year OS and ranked above all other treatments (Table). When adjusted for switching, all 3 CITs remained the highest-ranking treatments, with atezo ranked highest, followed by nivo and pembro. PFS and PD-(L)1 inhibitors’ population subgroup results will be shown.

Conclusions

This FP-NMA showed that PD-(L)1 inhibitors had the highest expected 5-year OS amongst 2L treatments and that factors such as switching affected OS benefit. These results, which vary from prior models, suggest that FP-NMA may be a more relevant and viable method for assessing LT clinical benefit in pts treated with CIT.

Clinical trial identification

Legal entity responsible for the study

F. Hoffmann-La Roche AG.

Funding

F. Hoffmann-La Roche AG.

Editorial Acknowledgement

Jeff Frimpter, Health Interactions.

Disclosure

C. Schulz: Advisory Role/Expert Testimony: AstraZeneca, Boehringer Ingelheim, Celgene, Lilly, MSD, Novartis, Roche; Honoraria: AstraZeneca, Boehringer Ingelheim, Celgene, Lilly, Novartis, Roche; Financing of Scientific Research: AstraZeneca, BMS, CellAct, Lilly, Novartis, Roche, Pfizer. P. Chu, C.G. Berardo, B. Karthuria: Employee: F. Hoffman-La Roche Ltd. J. Foo, C. Morel: Employee: Mapi Group (an ICON plc company), which received financial support from Roche. C. Watkins: Employee: Clarostat Consulting, which received financial support by Roche. M. Ballinger: Employee: Genentech Inc., a member of the Roche Group. D.R. Gandara: Grants and personal fees: Genentech Inc., a member of the Roche Group.Table: 1470P

Ranking outcomes of expected 5-year overall survival (intention-to-treat primary population of 850 pts from the OAK study; extended network including pembrolizumab)

	Unadjusted Analysis		Switching-Adjusted Analysis
	Median Rank (95% CrI)	SUCRA		Median Rank (95% CrI)	SUCRA
Nivolumab 3 mg/kg	2 (1, 9)	0.881	Atezolizumab 1200 mg	2 (1, 8)	0.903
Atezolizumab 1200 mg	3 (1, 10)	0.865	Nivolumab 3 mg/kg	3 (1, 9)	0.872
Pembrolizumab 2 mg/kg	3 (1, 13)	0.829	Pembrolizumab 2 mg/kg	3 (1, 14)	0.818
Docetaxel 40 mg/m² qw	7 (1, 18)	0.592	Ramucirumab + docetaxel 60 mg/m²	7 (1, 18)	0.594
Ramucirumab + docetaxel 60 mg/m²	7 (1, 18)	0.589	Docetaxel 40 mg/m² qw	7 (1, 18)	0.575
Erlotinib 150 mg	8 (3, 14)	0.570	Erlotinib 150 mg	8 (3, 14)	0.564
Ramucirumab + docetaxel 75 mg/m²	8 (2, 17)	0.547	Ramucirumab + docetaxel 75 mg/m²	8 (2, 17)	0.55
Erlotinib 300 mg	8 (1, 18)	0.533	Erlotinib 300 mg	8 (1, 18)	0.536
Pemetrexed or docetaxel	9 (2, 17)	0.519	Pemetrexed or docetaxel	9 (2, 17)	0.518
Docetaxel q3w pooled	9 (4, 15)	0.514	Nintedanib + docetaxel 75 mg/m²	9 (2, 17)	0.513
Nintedanib + docetaxel 75 mg/m²	9 (2, 17)	0.513	Docetaxel q3w pooled	9 (4, 16)	0.508
Paclitaxel poliglumex	9 (2, 18)	0.489	Paclitaxel poliglumex	10 (2, 18)	0.477
Docetaxel 75 mg/m²	11 (7, 15)	0.412	Docetaxel 75 mg/m²	11 (7, 15)	0.408
Docetaxel qw pooled	12 (5, 17)	0.379	Docetaxel qw pooled	12 (6, 17)	0.369
Pemetrexed 900 mg/m²	15 (4, 18)	0.259	Pemetrexed 900 mg/m²	14 (4, 18)	0.288
Pemetrexed 500 mg/m²	15 (8, 17)	0.239	Pemetrexed 500 mg/m²	14 (8, 17)	0.256
Placebo	16 (7, 18)	0.195	Placebo	16 (7, 18)	0.178
Pemetrexed 1000 mg/m²	18 (9, 18)	0.075	Pemetrexed 1000 mg/m²	18 (9, 18)	0.075

CrI, Credible interval; SUCRA, surface under the cumulative ranking curve; q3w, every 3 weeks; qw, once a week.

Poster display session: Biomarkers, Gynaecological cancers, Haematological malignancies, Immunotherapy of cancer, New diagnostic tools, NSCLC - early stage, locally advanced & metastatic, SCLC, Thoracic malignancies, Translational research

2680 - Fractional polynomial network meta-analysis: a different approach to indirectly assess the comparative efficacy of 2L+ cancer immunotherapy (CIT) treatments for metastatic NSCLC

Date

Session

Topics

Tumour Site

Presenters

Citation

Authors

Author affiliations

Resources

Abstract 2680

Background

Methods

Results

Conclusions

Clinical trial identification

Legal entity responsible for the study

Funding

Editorial Acknowledgement

Disclosure

Abstract 2680

Background

Methods

Results

Conclusions

Clinical trial identification

Legal entity responsible for the study

Funding

Editorial Acknowledgement

Disclosure

Resources from the same session