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. 2022 Mar 7:12:763926.
doi: 10.3389/fonc.2022.763926. eCollection 2022.

Interest of the Addition of Taxanes to Standard Treatment in First-Line Advanced HER2 Positive Gastroesophageal Adenocarcinoma in Selective Patients

Emeline Orillard  1   2 , Julie Henriques  2   3 , Dewi Vernerey  2   3 , Hamadi Almotlak  1 , Fabien Calcagno  1 , Francine Fein  4 , Serge Fratté  5 , Marine Jary  1   2 , Elodie Klajer  1 , Angelique Vienot  1   2 , Christophe Borg  1   2 , Stefano Kim  1   2   6
Affiliations

Interest of the Addition of Taxanes to Standard Treatment in First-Line Advanced HER2 Positive Gastroesophageal Adenocarcinoma in Selective Patients

Emeline Orillard et al. Front Oncol. .

Abstract

Background: Studies have reported a beneficial role of the addition of trastuzumab to platin-5-FU based chemotherapy in first-line advanced HER2 positive gastroesophageal adenocarcinoma (GEA). However, the effect of taxanes combined with platin-5FU + trastuzumab (PFT) is understudied.

Methods: We performed a retrospective cohort study to evaluate the interest of taxanes among HER2-positive advanced GEA patients treated with PFT. We enrolled HER2-positive advanced GEA patients who underwent treatment between January 2009 to March 2021 in seven hospitals centers in France, treated with PFT alone (S group) or with taxanes + PFT regimen (T group). The primary outcome was progression-free survival (PFS). Also, overall survival (OS), response rate, conversion surgery rate, and safety were evaluated.

Results: Overall, 65 patients received PFT-based therapy, 24 patients in the T group, and 41 patients in the S group. To avoid the selection bias, only those patients presenting an ECOG-PS of 0-1 and synchronous metastasis (21 patients in the T group and 19 patients in the S group) were included for analysis. The median PFS was 9.3 months (95%CI 7.0 to 17.2) in the T group and 5.9 months (95%CI 3.7 to 9.6) in the S group (log-rank p=0.038). Treatment by taxanes was significantly associated with a better PFS in univariate (HR 0.49; 95%CI 0.25 to 0.98, p=0.042) and multivariate Cox regression analysis (HR 0.44; 95%CI 0.21 to 0.94, p=0.033), and IPTW method (HR 0.56; 95% CI 0.34 to 0.91, p=0.019). OS was prolonged (19.0 months (95%CI 7.8 to 45.2) vs 13.0 months (95%CI 5.5 to 14.8), log-rank p=0.033) in favor of the T group. Treatment by taxanes was significantly associated with a better OS in univariate Cox regression analysis (HR 0.49; 95%CI 0.21 to 0.96, p=0.038) and IPTW method (HR 0.49; 95% CI 0.29 to 0.84, p=0.009). The response rate was higher in the T group, with conversion surgery in five patients. No treatment-related death was observed in both groups.

Conclusions: Given the improvement in PFS and OS, the addition of taxanes to standard chemotherapy could be considered as a promising treatment for selected HER2-positive advanced GEA patients, with PS 0-1 and synchronous metastasis (NCT04920747).

Keywords: HER2; gastric carcinoma; metastatic; survival; taxanes; trastuzumab.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
The hypothesis to combine taxanes to standard treatment in first-line advanced HER2 positive gastroesophageal adenocarcinoma.
Figure 2
Figure 2
Flowchart. S group: Standard regimen. T group: TPFT regimen. PS, Performance status.
Figure 3
Figure 3
Outcomes according to the treatment group in the population of analysis. Population of analysis: patients with ECOG PS 0 - 1 and synchronous metastasis. (A) Progression-Free Survival and (B) Overall Survival. S group: Standard regimen. T group: TPFT regimen. CI, Confidence Interval.
Figure 4
Figure 4
Outcomes according to conversion therapy in the T group of the population of analysis. Evaluation of progression-free survival and overall survival in the T group of the population of analysis (patients with ECOG PS 0 - 1 and synchronous metastasis). Conversion therapy corresponds to the resection of the primary tumor. Patients with conversion therapy have disease control after chemotherapy and local treatment of metastasis. CI, Confidence Interval; PFS, Progression-Free Survival; OS, Overall Survival.
See this image and copyright information in PMC

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