Here, we report two cases of advanced non-small cell lung cancer (NSCLC) in patients with negative driver genes who received ICI treatment for less than two years but continued to benefit from their administration after drug withdrawal. The first patient was diagnosed with left lung adenocarcinoma, cT1cN3M1c, stage IVb, and after four cycles achieved a completed response (CR). After 10 cycles of camrelizumab treatment, immunotherapy was discontinued because of hepatotoxicity. When the drug was discontinued, the curative effect was evaluated as CR. At the last follow-up, the drug withdrawal time had been more than 20 months, and the response was maintained at CR, with PFS of over 30 months. In the second case, the patient was diagnosed with left lung adenocarcinoma, cT1N3M1c, stage IVb. The patient was treated with sintilimab, and due to cardiac and skin toxicity, the patient withdrew from the trial after five cycles of immunotherapy. After drug withdrawal, the curative effect of the patients was maintained at PR. At the last follow-up, the drug withdrawal time was more than three months, and the curative effect was evaluated as PR. The PFS was more than nine months. In conclusion, whether the drug can be discontinued in advance after immune checkpoint inhibitor (ICI) therapy has been effective remains a concern, and at present there is no final conclusion in the medical profession. However, the results of this study indicate that early withdrawal of immunotherapy due to adverse reactions might also benefit patients with advanced lung adenocarcinoma with negative driver genes who achieve an early response to immunotherapy.