Successful re-challenge of PD-1 inhibitors in combination with bevacizumab and pemetrexed for multiple primary NSCLC progressing on prior PD-1 inhibitor therapy: one case report

Lung cancer is a malignant tumor with high incidence and mortality rates in China and worldwide. Approximately 10% of these diseases are caused by multiple primary non-small cell lung cancers (NSCLC). Traditional antitumor therapies, such as chemotherapy, radiotherapy, and targeted therapy, have limited efficacy in the treatment of advanced synchronous multiple primary NSCLC. Immunotherapy is considered the standard of care for advanced or recurrent NSCLC, however, approximately 60% of patients develop primary or secondary resistance to treatment. There are no standard recommendations for overcoming immune resistance. We describe a case of simultaneous multiple primary NSCLC in a patient who received programmed death factor-1 (PD-1) inhibitor monotherapy and developed brain metastases. After receiving second-line treatment with a combination of another PD-1 inhibitor, pemetrexed, and bevacizumab, the patient achieved complete remission, although they experienced grade 3 immune-related adverse reactions. Immune re-challenge is safe and feasible, and choosing a synergistic combination regimen is one of the options to overcome immune resistance. A larger sample size is needed to confirm the effectiveness and safety of this strategy in patients with NSCLC resistant to prior PD-1 inhibitors.