palbociclib combined with afatinib for advanced squamous carcinoma of esophagus or gastroesophageal junction

Conditions: Esophagus Squamous Cell Carcinoma

Summary: this is a prospective, multicenter, exploratory study. patients with advanced esophageal or gastro-esophageal junction squamous carcinoma who had progressed on first-line chemotherapy combined with immune checkpoint inhibitors were treated with cdk4/6 inhibitor palbociclib combined with afatinib. dose titration was used to determine the final dose, and objective antitumor efficacy was evaluated every 2 cycles (8 weeks +/- 7 days) according to recist 1.1 criteria, until tumor progression, intolerable toxicity, death, or withdrawal of informed consent. the primary endpoint is the objective response rate (orr).


Eligibility criteria:
inclusion criteria: * pathologically confirmed metastatic or inoperable locally advanced squamous carcinoma of the esophagus or gastroesophageal junction that is not amenable to radical radiotherapy. * prior progression to at least first-line chemotherapy which must include immune checkpoint inhibitors (except in patients with contraindications to immune checkpoint inhibitors). adjuvant/neoadjuvant therapy is allowed and is considered first-line therapy for advanced disease if recurrence occurs during or within 6 months of completion of adjuvant/neoadjuvant therapy. * at least one measurable tumor lesion according to recist v1.1 criteria. a lesion previously treated with radiotherapy is not acceptable as a target lesion unless the lesion 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; renal function: 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 experimental drugs * unable to swallow or under other circumstance which would drug absorption * other active malignant tumors, excluding those who have been disease free for more than 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 or hypertension 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) class iii or iv congestive heart failure in the past 12 months * known to be infected with human immunodeficiency virus (hiv), have acquired immunodeficiency syndrome (aids) related diseases, have active hepatitis b or hepatitis c * pregnant or nursing * may increase the risk associated with participation in the study or administration of the study drug or mental illness that may interfere with the interpretation of research results * there are other serious diseases that the researchers believe patients cannot be included in the study