Neoadjuvant pembrolizumab with paclitaxel and carboplatin in locally advanced esophageal and esophagogastric junction carcinoma: short-term outcomes of a single-center retrospective cohort

Abstract

Background: The addition of anti–PD-1 therapy to chemotherapy has become standard in advanced esophageal cancer and, as adjuvant nivolumab, after chemoradiotherapy and R0 resection. Its role in the neoadjuvant setting is still being defined, and real-world data from routine practice, particularly where chemoradiotherapy capacity is limited, remain sparse. We describe short-term outcomes of neoadjuvant pembrolizumab combined with paclitaxel and carboplatin in patients treated at a single center.
Methods: We retrospectively identified 14 consecutive patients with locally advanced esophageal or esophagogastric junction (EGJ) carcinoma who received neoadjuvant pembrolizumab 200 mg every 3 weeks with paclitaxel and carboplatin, with planned esophagectomy. The primary endpoint was pathological complete response (pCR, ypT0 ypN0). Secondary endpoints were the radiographic objective response, R0 resection, treatment completion, adverse events (CTCAE v5.0), postoperative morbidity, and short-term disease status. Continuous variables are summarized as median (range) and categorical variables as counts (percentages); no inferential testing was performed given the sample size.
Results: Twelve of 14 patients (85.7%) had squamous cell carcinoma; 9 (64.3%) had clinical stage III disease. All cycles were delivered as pembrolizumab plus paclitaxel–carboplatin; 6 patients (42.9%) completed all three planned cycles and 9 (64.3%) had at least one dose delay. A radiographic objective response was recorded in 9 patients (64.3%). Ten patients (71.4%) underwent esophagectomy, all with R0 resection; the four remaining patients did not proceed to surgery because of progressive disease (1), medical unfitness (2), or patient refusal (1). pCR occurred in 3 of 14 patients on an intention-to-treat basis (21.4%) and in 3 of 10 resected patients (30.0%); all three had had a complete clinical response and the highest PD-L1 combined positive scores in the cohort. Grade 3–4 adverse events occurred in 6 patients (42.9%) and immune-related adverse events in 5 (35.7%), including one grade 3 immune hepatitis and one grade 2 pneumonitis. After a median follow-up of 7.8 months (range 3.0–11.2), no deaths had occurred and two patients had developed recurrence.
Conclusions: In this small cohort, neoadjuvant pembrolizumab with paclitaxel and carboplatin was deliverable and permitted R0 resection in all operated patients, with a pCR rate consistent with early-phase neoadjuvant chemoimmunotherapy experience. Toxicity was not negligible and limited full-course delivery in more than half of patients. The sample size, absence of a comparator, and immature follow-up preclude conclusions about efficacy or survival; the findings are hypothesis-generating.