Background: ESCC is a health burden in Taiwan due to smoking and drinking habits. In R/M setting, the prognosis is worse. In 2021, KN590 study(pembrolizumab with chemotherapy in CPS≥10%), CM648 study(nivolumab with chemotherapy or nivolumab with ipilimumab in TPS≥1%), and ESCORt-1st study(camrelizumab with chemotherapy in TPS≥1%) have all been shown to get survival benefits compared with chemotherapy alone in front-line setting. Further immunotherapy combinations with targeted therapies and subsequent therapy options after anti-PD1 failure deserve more investigation. Methods: From early 2016 to late 2021, 26 advanced ESCC patients had ever received immunotherapy-containing regimens in Yun-lin Branch of National Taiwan University Hospital. We have reviewed basic characters, ICIs regimens, and treatment response of these patients. Results: 3 patients under progression during front-line KN590 got PR by subsequent afatinib(2) or lenvatinib(1) use. So, the overall response rate of advanced ESCC to immunotherapy-containing regimens was 59%(17/29) and disease control rate was 72%(21/29). Conclusions: Afatinib has multiple immuno-modulatory effects. AP or NA is an effective regimen in Taiwan, where double cancers, like HNSCC and ESCC, are popular due to smoking, drinking, and bêtel-nuts chewing. Following KN590 good efficacy was also seen in our institution and afatinib with anti-PD1 could be introduced in CT-unfit patients. In unresectable and/or oligometastatic ESCC, induction triple therapy may lead to conversion chemoradiation, even to final surgery. EGFR or VEGFR TKI with immunotherapy might also be a subsequent recue regimen after front-line anti-PD1 failure.