PD-1 monotherapy has progressed, and combination drugs should be carefully selected

With the continuous development of medicine, various methods in the field of tumor treatment are blooming, each playing an important role
.

How to reasonably and effectively combine these treatments to form targeted combination therapy, so that patients can better benefit from it, is the direction that researchers are exploring
.

But not all combinations can achieve the effect of "1+1>2"? For example, in patients with advanced lung cancer without EGFR and ALK driver gene mutations, the most common treatment is the use of PD-1 inhibitor-type immune drugs.
When the disease progresses in the later stage, chemotherapy is often used
.

However, some patients are reluctant to give up the previous immunotherapy, hoping to use the combination of immunotherapy and chemotherapy, and feel that the effect must be better than chemotherapy alone
.

Is this really true? The synergistic effect of immunotherapy and chemotherapy In the second-line treatment of advanced lung cancer, the general patient's disease progresses after platinum-containing chemotherapy, and the detection of EGFR and ALK driver gene mutations is negative, and immune monotherapy can be used, such as nivolio Monoclonal antibody, pembrolizumab, etc.
, but the response rate of patients with second-line single-agent immunotherapy is only 9%-14%
.

Regarding the reasons for the resistance of PD-1 and PD-L1 inhibitors, researchers believe that the infiltration of immune T cells around tumor cells is insufficient, antigen presentation is insufficient, or the immune suppressive microenvironment depletes T cells
.

An interesting study showed that if patients were initially treated with immune monotherapy followed by chemotherapy, the objective treatment response rate was very high
.

For this phenomenon, it was explained that after discontinuation of PD-1 or PD-L1 inhibitor drugs, due to the long half-life of these drugs, these inhibitors cause some activated immune cells to exist in the patient for a long time, so After subsequent chemotherapy, these T cells activated by the previous immune drug participated in the associated assist
.

However, there is also a phenomenon that the "immune imprint" left by the patient's previous use of PD-1 inhibitors does not remain for a long time
.

For this reason, the researchers conducted this study to test whether the combination of pembrolizumab with chemotherapy after progression on PD-1 monotherapy is more effective than chemotherapy alone
.

Is it "superfluous" to continue to use PD-1 immunotherapy after progress? This is a phase II clinical trial in patients with advanced EGFR and ALK driver gene mutation-negative lung cancer
.

The patient's disease progressed after receiving one or two chemotherapy regimens, at least one of which contained platinum
.

The use of immunomonotherapy after chemotherapy progression also progressed
.

Figure 1.
Survival with continued immunocombination chemotherapy after progression on immunotherapy monotherapy A total of 95 patients were included in this study, with a median follow-up of 10.
5 months
.

All patients were randomly divided into two groups: patients in the experimental group received the PD-1 inhibitor pembrolizumab in combination with chemotherapy, and patients in the control group received placebo in combination with chemotherapy
.

The median progression-free survival was 4.
1 months and 5.
9 months, respectively
.

The hazard ratio and overall survival were not statistically different
.

From Figure 1 you can't see any separation of the two curves, not much difference
.

Figure 2.
Survival of patients with high PD-L1 expression after progression on PD-1 monotherapy with immunocombination chemotherapy.
To further investigate this issue, the researchers reselected patients with high PD-L1 expression
.

For example, patients with a TPS score of PD-L1 greater than 50% tend to benefit more from immunotherapy
.

This group of patients also benefited better from previous PD-1 or PD-L1 inhibitors, with a clinically assessed partial response time of more than 6 months
.

For this group of patients, the two-year survival rate for pembrolizumab plus chemotherapy was 74%, compared with 38% for the placebo and chemotherapy group
.

From this point of view, patients with high PD-L1 expression will benefit from continued PD-1 combined chemotherapy
.

Enlightenment: How to choose treatment measures after the progress of immunotherapy The conclusion of the above research is: if the PD-L1 expression in tumor tissue samples is greater than 50%, and the tumor lesions are reduced by 30% during immune monotherapy, the state of partial remission lasts for 6 For more than one month, patients will benefit more by continuing to use the PD-1 inhibitor pembrolizumab in combination with chemotherapy after the progress of immune monotherapy
.

Otherwise, the combined PD-1 inhibitor pembrolizumab may not be required, and only single-agent chemotherapy is required
.

Figure 3.
With high PD-L1 expression, subsequent use of immunotherapy will benefit more.
Regarding immunotherapy and subsequent combined treatment measures, there will be more clinical trials and more new discoveries in the later stage
.

You are welcome to search and download the Cancer Degree APP to exchange anti-cancer experience with many similar patients
.

Reference: Hyun Ae Jung, et al.
, Continuation of pembrolizumab with additional chemotherapy after progression with PD-1/PD-L1 inhibitor monotherapy in patients with advanced non-small cell lung cancer: a randomized, placebo-controlled phase II study, Clin Cancer Res.
2022 Jan 31.
Click below to learn more about the selected anti-cancer and anti-cancer dry goods of clinical trial projects-Swipe left and right to see more-