Triplet chemo bests doublet regimen for ESCC

A triplet chemotherapeutic (CT) regimen comprising docetaxel, cisplatin, and 5-fluororacil (5-FU; DCF) outdid a doublet regimen comprising CF as neoadjuvant treatment for locally advanced oesophageal squamous cell carcinoma (ESCC), the phase III JCOG*1109 NExT study suggests.

 

“Most [oesophageal cancer (EC)] patients are diagnosed at an advanced stage, and preoperative therapy followed by surgery is recommended for locally advanced EC, but the prognosis remains poor,” said Dr Ken Kato from the National Cancer Center Hospital, Tokyo, Japan, during his presentation at ASCO GI 2022.

 

Neoadjuvant CF is the current standard of treatment for locally advanced EC in Japan. [Ann Surg Oncol 2021;19:68–74] “However, the optimal modality of neoadjuvant treatment for locally advanced ESCC is unclear,” said Kato.

 

A total of 601 individuals with ESCC (median age 65 years, 88 percent male) were randomized 1:1:1 to receive neoadjuvant CF, DCF, or CF augmented with radiation therapy (CF-RT)*. More than two-thirds (70 percent) of patients had medial thoracic ESCC and 61 percent had clinical stage III disease. All participants underwent thoracic oesophagectomy with regional lymphadenectomy. Minimum follow-up was 36 months. [ASCO GI, abstract 238]

 

In terms of the primary endpoint of overall survival (OS), DCF showed superiority over CF (median not reached [NR] vs 5.6 years; hazard ratio [HR], 0.68; p=0.006). The comparison between CF and CF-RT did not yield statistical significance (median 5.6 vs 7 years; HR, 0.84; p=0.12). Three-year OS rates for the respective DCF, CF, and CF-RT arms were 72, 63, and 68 percent.

 

A similar trend in favour of DCF was seen in terms of progression-free survival compared with CF (median NR vs 2.7 years; HR, 0.67). The comparison between CF and CF-RT yielded an HR of 0.77 (median 2.7 vs 5.3 years).

 

Survival outcomes generally favoured DCF over CF across most subgroups evaluated, added Kato.

 

The most common grade 3–4 adverse events (AEs) associated with DCF were neutropenia (85 percent), leukocytopenia (64 percent), and hyponatremia (26 percent). For CF-RT, the most common AEs were leukocytopenia (54 percent) followed by loss of appetite (15 percent). Most AEs were manageable, noted Kato.

 

About two-thirds of the overall cohort underwent three lymph node dissection, and >90 percent achieved R0 resection (90, 94, and 99 percent in the respective CF, DCF, and CF-RT arms). The most common grade ≥2 postoperative complication was recurrent laryngeal nerve paralysis (15, 10, and 10 percent, respectively).

 

Regarding pathological outcomes, more participants on DCF achieved a grade 3 (no residual tumour) histologic response of primary site based on the Japanese classification of oesophageal cancer as opposed to those who received CF (22 percent vs 2 percent). A similar trend favouring DCF over CF was seen in terms of pathologic complete response rate (19 percent vs 2 percent).

 

“[Our findings showed that] neoadjuvant DCF significantly improved OS compared with CF as neoadjuvant therapy for locally advanced ESCC, with a manageable toxicity profile. DCF represents a new standard neoadjuvant treatment for ESCC,” concluded Kato.