Abstract 4847
Background
The impact of oncology drug regulatory approvals on population-level patient (pt) outcomes is often unknown. Before targeted therapies, chemotherapy treatment of stage IV melanoma resulted in minimal OS improvement. To understand how PD-1 inhibitor approval influenced OS in treatment eligible stage IV melanoma pts, we assessed OS before and after the US Food and Drug Administration approval date of pembrolizumab (P), a second generation (2nd gen) immune checkpoint inhibitor (ICI), in a cohort treated with targeted therapies.
Methods
US-based pts diagnosed with stage IV melanoma from 1/1/2011 to 3/31/2019 and receiving BRAF/MEK inhibitors or ICI in first-line (1L) in the deidentified nationwide Flatiron Health electronic health record-derived database were eligible. We used a multivariable Cox model indexed to 1L start and adjusted for age. Follow-up time relative to approval of P (9/4/2014) was a time-varying covariate.
Results
Of 882 pts, 692 (78.5%) started 1L after P approval. Of those, 40.6% (n = 281) received 2nd gen ICI and 27.3% (n = 189) received combination ICI therapy in 1L. During pre-approval, 56.3% (n = 107) received 1L first gen ICI (CTLA-4 inhibitor). Pre-approval pts were younger than post-approval pts (median 64.0 [IQR: 57.0, 72.8] vs 68.0 yrs [IQR: 58.8, 77.0]; p < 0.001) but similar in other clinical and demographic characteristics. In unadjusted analyses, median OS was twice as long for post-approval pts compared to pre-approval pts (14.0 mos [95% CI: 11.6, 17.5] vs 6.7 [95% CI: 5.5, 9.2]; log rank = 0.001). In the multivariable time-varying model, mortality risk decreased by 22% (HR = 0.78 [95% CI: 0.62, 0.98]; p = 0.035) following P approval. When comparing treatments during post-approval, unadjusted median OS was 8 mos longer in pts receiving combination ICI relative to those treated with 2nd gen ICI monotherapy in 1L (20.6 mos [95% CI: 14.0, not reached] vs 12.7 mos [95% CI: 9.7, 17.5]; log rank = 0.069).
Conclusions
Introduction of 2nd gen ICI therapy was associated with longer OS in stage IV melanoma pts treated with targeted therapies. Future analyses could assess outcomes relative to regulatory approvals for specific subpopulations, such as those who would have been excluded from trials.
Clinical trial identification
Editorial acknowledgement
Legal entity responsible for the study
Flatiron Health, Inc.
Funding
Flatiron Health, Inc., independent subsidiary of the Roche group.
Disclosure
A.Z. Torres: Full / Part-time employment: Flatiron Health, Inc., which is an independent subsidiary of the Roche Group; Shareholder / Stockholder / Stock options: Flatiron Health Inc. (initiated before acquisition by Roche in April 2018); Shareholder / Stockholder / Stock options: Roche. R. Mathur: Shareholder / Stockholder / Stock options: Roche; Full / Part-time employment: Flatiron Health, Inc., which is an independent subsidiary of the Roche Group. K. Maignan: Full / Part-time employment: Flatiron Health, Inc., which is an independent subsidiary of the Roche Group; Full / Part-time employment: Roche; Shareholder / Stockholder / Stock options: Flatiron Health Inc. (initiated before acquisition by Roche in April 2018). M. Tucker: Shareholder / Stockholder / Stock options: Flatiron Health Inc. (initiated before acquisition by Roche in April 2018); Shareholder / Stockholder / Stock options: Roche; Shareholder / Stockholder / Stock options: Flatiron Health, Inc., which is an independent subsidiary of the Roche Group. K.J. Ciofalo: Shareholder / Stockholder / Stock options: Flatiron Health Inc. (initiated before acquisition by Roche in April 2018); Shareholder / Stockholder / Stock options: Roche; Full / Part-time employment: Flatiron Health, Inc., which is an independent subsidiary of the Roche Group. K.R. Carson: Full / Part-time employment: Flatiron Health, Inc., which is an independent subsidiary of the Roche Group; Shareholder / Stockholder / Stock options: Roche; Shareholder / Stockholder / Stock options: Flatiron Health Inc. (initiated before acquisition by Roche in April 2018). All other authors have declared no conflicts of interest.
Resources from the same session
1084 - Dissociated responses in patients with metastatic solid tumors treated with immunotherapy
Presenter: Pauline Vaflard
Session: Poster Display session 3
Resources:
Abstract
4600 - Patterns and outcomes related to rapid progressive disease in a cohort of advanced solid tumors treated with immune checkpoint inhibitors (ICIs).
Presenter: Lucio Ghiglione
Session: Poster Display session 3
Resources:
Abstract
3547 - Real World Outcomes of Immune-Related Adverse Events (irAEs) among Patients Receiving Immune Checkpoint Inhibitors (ICIs) in Hospital Settings
Presenter: Saby George
Session: Poster Display session 3
Resources:
Abstract
1124 - Sex-based heterogeneity of efficacy of anticancer immunotherapy
Presenter: Fabio Conforti
Session: Poster Display session 3
Resources:
Abstract
4133 - Comparative efficacy and safety of PD-1/PD-L1 inhibitors for patients with solid tumors: a systematic review and Bayesian network meta-analysis
Presenter: Qingyuan Huang
Session: Poster Display session 3
Resources:
Abstract
2548 - Excess weight and efficacy of anti-PD-1 antibodies in advanced cancer patients
Presenter: Jacobo Rogado
Session: Poster Display session 3
Resources:
Abstract
2228 - Safety and efficacy of anti-PD-1 inhibitor ABBV-181 in lung and head and neck carcinoma
Presenter: Antoine Italiano
Session: Poster Display session 3
Resources:
Abstract
2333 - Efficacy and safety of immune checkpoint inhibitors (ICIs) for treatment of advanced solid tumours in octogenarian patients
Presenter: Soraya Mebarki
Session: Poster Display session 3
Resources:
Abstract
2215 - Clinical outcomes of immune checkpoint inhibitors in older and younger patients with advanced solid tumours in a real-life setting
Presenter: Pauline Corbaux
Session: Poster Display session 3
Resources:
Abstract
2881 - Impact of corticosteroids and antibiotics on efficacy of immune-checkpoint inhibitors in advanced non-small cell lung cancer
Presenter: Joaquin Mosquera Martinez
Session: Poster Display session 3
Resources:
Abstract