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

Overview

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

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