Heavy! PD-1 “oligo-drug resistance” research has made significant progress, and local treatment has greatly improved patient survival

Immunotherapy has given many advanced cancer patients the hope of a cure, but about half of the initial treatment is still effective. The patient developed acquired resistance, which progressed again after remission. How to treat cancer patients after PD-1 resistance has always been a hot topic, and we have also made related reports (Reference: PD-1 resistance is saved! Five latest clinical programs, can significantly improve the survival of drug-resistant patients). However recently, MSKCC’s Adam J.
A study by Schoenfeld
et al pointed out that after PD-1 acquired drug resistance, most patients may not need to change the treatment method, and ablation therapy can be done for the advanced lesions.
[1]. They analyzed 143 patients with metastatic non-small cell lung cancer who developed resistance to PD-(L)1 in MSKCC and found that most of them were Oligo-acquired drug resistance with ≤3 progressive lesions. Patients with oligodrug resistance can be effectively controlled by local treatments such as surgery and radiotherapy, reducing the risk of death by 59%. To date, 13 patients have sustained remission for more than 2 years after topical therapy. the acquired drug resistance of tumors has been A difficult problem is that under the selective pressure of anticancer drugs, cancer cells will spontaneously evolve drug resistance, leading to disease progression. For example, the commonly used EGFR inhibitor in lung cancer, although the initial efficacy is very good, but it will inevitably develop resistance in about 2 years, and can only be switched to the next generation medicine. Although immunotherapy has the characteristics of long-term benefits, and some patients can even be cured, 50% of the initially effective patients will develop acquired drug resistance, leading to further progression of the disease. However, there are many differences between progression and progression, such as the number of lesions that progress. In some patients, after drug resistance, only a few lesions progressed in the whole body, and some patients directly developed a large number of new lesions. What are the differences between these two types of progress? researchers at MSK )1 inhibitor-treated 1536 non-small cell lung cancer patients were analyzed. Of these patients, 312 were in remission after treatment, and 143 of them developed acquired resistance and their disease progressed again. By the number of lesions that progressed, 49 of these patients had 1 progressive lesion, 20 had 2, 11 had 3, and 63 had 4 or more advanced lesions. There was no significant difference in survival after progression among patients with oligodrug resistance with 1, 2, or 3 lesions. However, compared with patients with systemic drug resistance with ≥4 lesions, the survival time of patients with oligodrug resistance was significantly longer, with a median survival of 28 months after disease progression, compared with only 10 months for patients with systemic drug resistance. oligodrug-resistant patients live longer >In addition to survival, the two groups of patients also had many differences in characteristics. Compared with patients with systemic drug resistance, the tumor mutation burden of patients with oligodrug resistance is significantly higher, which is nearly twice that of patients with systemic drug resistance, and the effect of initial treatment is also better. In addition, the progression of patients with oligodrug resistance is mostly the emergence of new lesions, while the patients with systemic drug resistance are mostly the recurrence of existing lesions. After progression, 57 of 80 oligodrug-resistant patients underwent local therapy, including radiotherapy, surgery, and radioembolization, and 56 of them continued to use their original PD- (L)1 inhibitor. Patients who received topical therapy had a 52% lower risk of death than patients who did not receive topical therapy. Patients who received local therapy lived longer after progression than those who received systemic therapy only At the time of data cutoff, 58% of patients with oligodrug resistance were still using PD-(L)1 inhibitors. Among them, 13 patients who received local therapy had been in remission for 2 years The above, there is no further progress.The researchers said that there may be essential differences between patients with oligodrug resistance and patients with systemic drug resistance, and further research on these two types is needed. patient-to-patient differences and to identify the best treatment for patients with different numbers and locations of lesions.

References:< /span>[1]. Schoenfeld A J,
Rizvi H A, Memon D, et al. Systemic and oligo-acquired resistance to PD-(L) 1
blockade in lung cancer[J]. Clinical Cancer Research, 2022.