Amivantamab was the first approved therapy for advanced/metastatic NSCLC harboring EGFR exon 20 insertion mutations (Ex20ins) who progressed on platinum chemotherapy (CT). Since Ex20ins is uncommon, it may be confused with activating EGFR mutations resulting in treatment with limited benefit. This study estimates the relative effectiveness of amivantamab versus alternative anti-cancer treatments used in real-world settings for NSCLC with Ex20ins.
Data from the single-arm CHRYSALIS trial were compared to an external cohort of patients derived from six US and European real-world data sources that met the CHRYSALIS Cohort D+ eligibility criteria. Amivantamab was compared to EGFR TKIs including osimertinib, immunotherapy, non-platinum CT, VEGFi + CT, and others. Patient-level data were used to adjust for differences in prognostic factors using inverse probability weighting (average treatment effect among the treated). Binary and time-to-event endpoints were analyzed using weighted logistic regression and proportional hazards regression, respectively.
After adjustment, baseline characteristics between the two cohorts were balanced. For all individual treatment class comparisons, results were consistently in favor of amivantamab in overall survival (OS), progression free survival (PFS), time to next treatment (TTNT), and overall response rate by investigator (ORR-INV) (see
| Treatment | Adjusted Hazard Ratio (95% CI) for amivantamab vs. other treatment | ||||
|---|---|---|---|---|---|
| N | ORR-INV | OS | PFS-INV | TTNT | |
| Amivantamab | 114 | 36.8% | – | – | – |
| All EGFR TKIs | 69 | 5.3% | 0.46 (0.30, 0.72) | 0.51 (0.34, 0.76) | 0.38 (0.26, 0.55) |
| Osimertinib subgroup | 22 | 0.0% | 0.37 (0.19, 0.73) | 0.67 (0.33, 1.37)^ | 0.55 (0.31, 0.98) |
| Immunotherapy | 91 | 13.2% | 0.40 (0.27, 0.60) | 0.42 (0.31, 0.58) | 0.41 (0.29, 0.57) |
| Non-platinum chemotherapy | 87 | 18.1% | 0.45 (0.29, 0.70) | 0.52 (0.36, 0.76) | 0.36 (0.25, 0.53) |
| VEGFi + chemotherapy | 57 | 21.4%^ | 0.54 (0.34, 0.85) | 0.60 (0.42, 0.87) | 0.53 (0.35, 0.79) |
| Other | 79 | 27.2% | 0.58 (0.36, 0.92) | 0.61 (0.43, 0.87) | 0.51 (0.35, 0.75) |
No statistically significant difference vs. amivantamab; all other values significant.
Based on this adjusted treatment comparison, amivantamab provides significant benefits compared to alternative therapies used in real world practice. Education on appropriate treatment choice is important to advance quality of cancer care.
The authors acknowledge Heather Burnett of Evidera, a ThermoFisher company, for medical writing and ediotrial assistance based on the author's input and direction.
The authors.
Janssen.
N. Girard: Financial Interests, Personal, Invited Speaker: AstraZeneca, BMS, MSD, Roche, Pfizer, Mirati, Amgen, Novartis, Sanofi; Financial Interests, Personal, Advisory Board: AstraZeneca, BMS, MSD, Roche, Pfizer, Janssen, Boehringer Ingelheim, Novartis, Sanofi, AbbVie, Amgen, Eli Lilly, Grunenthal, Takeda, Owkin; Financial Interests, Institutional, Research Grant, Local: Roche, Sivan, Janssen; Financial Interests, Institutional, Funding: BMS; Non-Financial Interests, Personal, Officer, International Thymic malignancy interest group, president: ITMIG; Other, Personal, Other, Family member is an employee: AstraZeneca. J. Wolf: Financial Interests, Personal, Advisory Board: Amgen, AstraZeneca, Blueprint, BMS, Boehringer Ingelheim, Daiichi Sankyo, Ignyta, Janssen, Eli Lilly, Loxo, MSD, Novartis, Pfizer, Roche, Seattle Genetics, Takeda; Financial Interests, Personal, Invited Speaker: Bayer, Chugai; Financial Interests, Institutional, Research Grant: BMS, Janssen, Novartis, Pfizer. T.M. Kim: Non-Financial Interests, Personal, Advisory Board: AstraZeneca, Janssen, Regeneron, Takeda; Financial Interests, Personal, Invited Speaker: AstraZeneca, IMBDx, Inc., Takeda, Yuhan; Financial Interests, Personal, Advisory Role: AstraZeneca, Janssen, Regeneron, Samsung Bioepis, Takeda, Yuhan; Financial Interests, Personal, Research Grant: AstraZeneca-KHIDI; Non-Financial Interests, Institutional, Writing Engagements: AbbVie, AstraZeneca, Bayer, Black Diamond Therapeutics, Blueprint Medicines, Boryung, Bristol Myers Squibb, Celgene, F. Hoffman-La Roche Ltd/Genentech, Inc., Hanmi, Janssen, Novartis, Regeneron, Sanofi; Non-Financial Interests, Institutional, Invited Speaker: Takeda, Yuhan. N. Leighl: Financial Interests, Personal, Other, CME/independent lectures: MSD, BMS, Hoffmann LaRoche, EMD Serono; Financial Interests, Personal, Invited Speaker, independent lectures: Novartis, Takeda; Financial Interests, Personal, Advisory Board: Puma Biotechnology; Financial Interests, Institutional, Research Grant: Amgen, AstraZeneca, Array, Bayer, EMD Serono, Guardant Health, Eli Lilly, MSD, Pfizer, Roche, Takeda. T. Li: Financial Interests, Personal, Stocks/Shares: Janssen; Financial Interests, Personal, Full or part-time Employment: Janssen. J. Cabrieto: Financial Interests, Personal, Stocks/Shares: Janssen; Financial Interests, Personal, Full or part-time Employment: Janssen. J. Diels: Financial Interests, Personal, Stocks/Shares: Janssen; Financial Interests, Personal, Full or part-time Employment: Janssen. J. Sermon: Financial Interests, Personal, Stocks/Shares: Janssen; Financial Interests, Personal, Full or part-time Employment: Janssen. P. Mahadevia: Financial Interests, Personal, Stocks/Shares: Janssen; Financial Interests, Personal, Full or part-time Employment: Janssen. C.A. Schioppa: Financial Interests, Personal, Stocks/Shares: Janssen; Financial Interests, Personal, Full or part-time Employment: Janssen. J. Sabari: Financial Interests, Personal, Advisory Board: AstraZeneca, Genentech, Janssen, Pfizer, Regeneron, Sanofi Genzyme, Takeda, Mirati Therapeutics. All other authors have declared no conflicts of interest.