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. 2023 Nov 8;15(22):5326.
doi: 10.3390/cancers15225326.

Amivantamab Compared with Real-World Physician's Choice after Platinum-Based Therapy from a Pan-European Chart Review of Patients with Lung Cancer and Activating EGFR Exon 20 Insertion Mutations

Petros Christopoulos  1   2 , Nicolas Girard  3   4 , Claudia Proto  5 , Marta Soares  6 , Pilar Garrido Lopez  7 , Anthonie J van der Wekken  8 , Sanjay Popat  9   10 , Joris Diels  11 , Claudio A Schioppa  11 , Jan Sermon  11 , Nora Rahhali  12 , Corinna Pick-Lauer  13 , Agnieszka Adamczyk  14 , James Penton  15 , Marie Wislez  16
Affiliations

Amivantamab Compared with Real-World Physician's Choice after Platinum-Based Therapy from a Pan-European Chart Review of Patients with Lung Cancer and Activating EGFR Exon 20 Insertion Mutations

Petros Christopoulos et al. Cancers (Basel). .

Abstract

Patients with advanced non-small cell lung cancer (NSCLC) with epidermal growth factor receptor gene (EGFR) Exon 20 insertions (Exon20ins) at the second line and beyond (2L+) have an unmet need for new treatment. Amivantamab, a bispecific EGFR- and MET-targeted antibody, demonstrated efficacy in this setting in the phase 1b, open-label CHRYSALIS trial (NCT02609776). The primary objective was to compare the efficacy of amivantamab to the choices made by real-world physicians (RWPC) using an external control cohort from the real-world evidence (RWE) chart review study, CATERPILLAR-RWE. Adjustment was conducted to address differences in prognostic variables between cohorts using inverse probability weighting (IPW) and covariate adjustments based on multivariable regression. In total, 114 patients from CHRYSALIS were compared for 55 lines of therapy from CATERPILLAR-RWE. Baseline characteristics were comparable between the amivantamab and IPW-weighted RWPC cohorts. For amivantamab versus RWPC using IPW adjustment, the response rate ratio for the overall response was 2.14 (p = 0.0181), and the progression-free survival (PFS), time-to-next-treatment (TTNT) and overall survival (OS) hazard ratios (HRs) were 0.42 (p < 0.0001), 0.47 (p = 0.0063) and 0.48 (p = 0.0207), respectively. These analyses provide evidence of clinical and statistical benefits across multiple outcomes and adjustment methods, of amivantamab in platinum pre-treated patients with advanced NSCLC harboring EGFR Exon20ins. These results confirm earlier comparisons versus pooled national registry data.

Keywords: EGFR Exon 20 insertion mutations; adjusted comparison; amivantamab; non-small cell lung cancer; real-world physician’s choice.

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Conflict of interest statement

As stated above, this research was funded by Janssen Pharmaceutica NV. All Janssen authors contributed to the design of the study, the collection, analysis and interpretation of data, the writing of the manuscript, and the decision to publish the results. Petros Christopoulos: Research funding from AstraZeneca, Amgen, Boehringer Ingelheim, Novartis, Roche, and Takeda; advisory board/speaker’s honoraria from AstraZeneca, Boehringer Ingelheim, Chugai, Daiichi Sankyo, Eli Lilly, Gilead, Janssen, MSD, Novartis, Pfizer, Roche, Takeda, and Thermo Fisher; all outside the submitted work. Nicolas Girard: Consulting/advisory role for AbbVie, AstraZeneca, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Janssen, MSD, Novartis, Pfizer, PharmaMar, Roche, Sanofi, and Takeda; travel, accommodations, expenses for AstraZeneca, BMS, MSD Oncology, and Roche; research funding from AstraZeneca, Boehringer Ingelheim, and Roche. Claudia Proto: Consulting/advisory role for AstraZeneca, Bristol-Myers Squibb, Janssen, MSD, Roche, and Sanofi; travel, accommodation, expenses for AstraZeneca, Bristol-Myers Squibb, MSD, and Roche; institutional research funding from AstraZeneca, Eli Lilly Roche, MSD, Spectrum Pharmaceutical, Janssen, and Pfizer. Marta Soares: Consulting/advisory role for AstraZeneca, Bristol-Myers Squibb, Boehringer Ingelheim Janssen, Eli Lilly, Merck Serono, MSD, Novartis, Pfizer, Roche, and Takeda. Pilar Garrido Lopez: Consultancy/honoraria from AbbVie, Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Janssen, MSD, Novartis, Pfizer, Roche, Sanofi, and Takeda; direct funding from Medscape and Touch Medical; institutional research funding from Amgen, AstraZeneca, Blueprint, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Janssen, IO Biotech, MSD, Roche, and Takeda. Anthonie J. van der Wekken: Grants and personal fees from AstraZeneca, Boehringer Ingelheim, Janssen, Pfizer, Roche, and Takeda; personal fees from Amgen, Lilly, and Merck; outside the submitted work and all payments to the UMCG. Sanjay Popat: Consultancy/honoraria from Amgen, AstraZeneca, Bayer, BeiGene, Blueprint, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, EQRx, GlaxoSmithKline, Guardant Health, Janssen, Merck KGaA, MSD, Novartis, Pfizer, Roche, Sanofi, Seattle Genetics, Takeda, and Turning Point Therapeutics; direct funding from Elsevier, Medscape, Touch Medical, and VJ Oncology; institutional research funding from Amgen, AstraZeneca, Blueprint, Boehringer Ingelheim, Bristol-Myers Squibb, Daiichi Sankyo, Eli Lilly, GlaxoSmithKline, Guardant Health, Janssen, MSD, Roche, Takeda, Seattle Genetics, Trizel, and Turning Point Therapeutics. Joris Diels: Employee of Janssen and shareholder of Johnson & Johnson. Claudio A. Schioppa: Employee of Janssen and shareholder of Johnson & Johnson. Jan Sermon: Employee of Janssen and shareholder of Johnson & Johnson. Nora Rahhali: Employee of Janssen and shareholder of Johnson & Johnson. Corinna Pick-Lauer: Employee of Janssen. Agnieszka Adamczyk: Employee of Janssen and shareholder of Johnson & Johnson. James Penton: Employee of Janssen and shareholder of Johnson & Johnson. Marie Wislez: Consulting/advisory role from AstraZeneca, Bristol-Myers Squibb, Eli Lilly, MSD, Novartis, Pfizer, Roche, and Takeda; travel, accommodations, expenses from AstraZeneca, Bristol-Myers Squibb, MSD, and Roche.

Figures

Figure 1
Figure 1
Forest plot of the OR for ORR and CHRYSALIS versus the CATERPILLAR-RWE cohort (amivantamab vs. RWPC)—multivariable regression. *** Percentage was computed as the number of events/N. Percentages presented for ‘N Amivantamab’ and ‘N RWPC’ were rounded. One patient in the RWPC cohort had no information on response and was, therefore, excluded from the analysis of ORR. An OR of the relative treatment effect (first row) greater than 1 favored amivantamab. For each covariate included in the multivariable model, the first level was used as a reference. For the other levels of each covariate, an OR greater than 1 favored improved outcomes relative to the reference category, while accounting for the effect of all other covariates. The square box represents the point estimate, with the horizontal line representing the 95% CIs. CI: confidence interval; ECOG: Eastern Cooperative Oncology Group; HR: hazard ratio; OR: odds ratio; ORR: overall response rate; RWPC: real-world physician’s choice.
Figure 2
Figure 2
Kaplan–Meier curve for PFS of CHRYSALIS versus CATERPILLAR-RWE (amivantamab versus RWPC)—unadjusted and IPW (ATT)-adjusted. ATT: average treatment effect among the treated; CI: confidence interval; HR: hazard ratio; IPW: inverse probability weighting; PFS: progression-free survival; RWPC: real-world physician’s choice.
Figure 3
Figure 3
Forest plot of the HR of PFS for CHRYSALIS versus CATERPILLAR-RWE (amivantamab versus RWPC)—multivariable regression. Percentages presented for ‘N Amivantamab’ and ‘N RWPC’ are rounded. An HR of the relative treatment effect (first row) lower than 1 favors amivantamab. For each covariate included in the multivariable model, the first level is used as a reference. For the other levels of each covariate, an HR lower than 1 favors improved outcomes relative to the reference category while accounting for the effect of all other covariates. The square box represents the point estimate, with the horizontal line representing the 95% CIs. CI: confidence interval; ECOG: Eastern Cooperative Oncology Group (performance status); HR: hazard ratio; PFS: progression-free survival; RWPC: real-world physician’s choice.
Figure 4
Figure 4
Kaplan–Meier curve of TTNT for CHRYSALIS versus CATERPILLAR-RWE (amivantamab versus RWPC)—unadjusted and IPW (ATT)-adjusted. ATT: average treatment effect among the treated; CI: confidence interval; HR: hazard ratio; IPW: inverse probability weighting; RWPC: real-world physician’s choice; TTNT: time-to-next treatment.
Figure 5
Figure 5
Forest plot of the HR of TTNT for CHRYSALIS versus CATERPILLAR-RWE (amivantamab versus RWPC)—multivariable regression. Percentages presented for ‘N Amivantamab’ and ‘N RWPC’ are rounded. An HR of the relative treatment effect (first row) lower than 1 favors amivantamab. For each covariate included in the multivariable model, the first level is used as a reference. For the other levels of each covariate, an HR lower than 1 favors improved outcomes relative to the reference category while accounting for the effect of all other covariates. The square box represents the point estimate, with the horizontal line representing the 95% CIs. CI: confidence interval; ECOG: Eastern Cooperative Oncology Group (performance status); HR: hazard ratio; RWPC: real-world physician’s choice; TTNT: time-to-next treatment.
Figure 6
Figure 6
Kaplan–Meier curve of OS for CHRYSALIS versus CATERPILLAR-RWE (amivantamab versus RWPC)—unadjusted and IPW (ATT)-adjusted. ATT: average treatment effect among the treated; CI: confidence interval; HR: hazard ratio; IPW: inverse probability weighting; OS: overall survival; RWPC: real-world physician’s choice.
Figure 7
Figure 7
Forest plot of the HR for OS for CHRYSALIS versus CATERPILLAR-RWE (amivantamab versus RWPC)—multivariable regression. Percentages presented for ‘N Amivantamab’ and ‘N RWPC’ are rounded. An HR of the relative treatment effect (first row) lower than 1 favors amivantamab. For each covariate included in the multivariable model, the first level is used as a reference. For the other levels of each covariate, an HR lower than 1 favors improved outcomes relative to the reference category, while accounting for the effect of all other covariates. The square box represents the point estimate, with the horizontal line representing the 95% CIs. CI: confidence interval; ECOG: Eastern Cooperative Oncology Group (performance status); HR: hazard ratio; OS: overall survival; RWPC: real-world physician’s choice.
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