Palbociclib Combined With Afatinib for Advanced Squamous Carcinoma of Esophagus or Gastroesophageal Junction

Inclusion Criteria:

• Pathologically confirmed metastatic or inoperable locally advanced squamous carcinomaof the esophagus or gastroesophageal junction that is not amenable to radicalradiotherapy.
• Prior progression to at least first-line chemotherapy which must include immunecheckpoint inhibitors (except in patients with contraindications to immune checkpointinhibitors). Adjuvant/neoadjuvant therapy is allowed and is considered first-linetherapy for advanced disease if recurrence occurs during or within 6 months ofcompletion of adjuvant/neoadjuvant therapy.
• At least one measurable tumor lesion according to RECIST V1.1 criteria. A lesionpreviously treated with radiotherapy is not acceptable as a target lesion unless thelesion is significantly progressive.
• Sign the informed consent form
• 18~75 years
• Performance status: ECOG 0-1
• Good organ function: Blood routine: hemoglobin ≥90g/L, neutrophil ≥1.5×10^9/L, platelet ≥100×10^9/L; Renalfunction: creatinine≤1.5×upper limit of normal (UNL) or creatinine clearance ≥50ml/min;Liver function: total bilirubin (TBIL)≤1.5×upper limit of normal (UNL); ALT≤2.5×UNL,AST≤2.5×UNL; Ejection fraction at least 50% (or lower limit of normal) by echocardiogram

Exclusion Criteria:

• Other pathological category, such as adenocarcinoma, adenosquamous carcinoma
• Have received CDK4/6 inhibitors or anti-EGFR targeted drugs in the past
• Known to have allergic reactions to any ingredients or excipients of experimentaldrugs
• Unable to swallow or under other circumstance which would drug absorption
• Other active malignant tumors, excluding those who have been disease free for morethan 5 years or in situ cancer considered to have been cured by adequate treatment
• Diabetes was not controlled, defined as HbA1c > 7.5% after anti-diabetic drugs orhypertension was not controlled, defined as systolic / diastolic blood pressure > 140 / 90 mmHg after antihypertensive drug
• Myocardial infarction, severe/unstable angina, New York Heart Association (NYHA) classIII or IV congestive heart failure in the past 12 months
• Known to be infected with human immunodeficiency virus (HIV), have acquiredimmunodeficiency syndrome (AIDS) related diseases, have active hepatitis B orhepatitis C
• Pregnant or nursing
• May increase the risk associated with participation in the study or administration ofthe study drug or mental illness that may interfere with the interpretation ofresearch results
• There are other serious diseases that the researchers believe patients cannot beincluded in the study