How to treat survival longer after surgery for early lung cancer?

In order to reduce the risk of postoperative recurrence, researchers have made various attempts, for lung cancer patients with EGFR gene mutations, is it better to use targeted drugs or PD-1 inhibitors after surgery? Can PD-1 inhibitors be used postoperatively in patients without driver gene mutations? What about the improvement? In response to these questions, a recent study published in the internationally renowned academic journal "Lancet Oncology" gives us the answer

Status of postoperative treatment of early-stage lung cancer

According to the American Joint Cancer Council (AJCC) Staging System (7th Edition), the standard treatment for stage IB to IIIA non-small cell lung cancer is surgical resection followed by adjuvant chemotherapy

In the ADAURA7 study, for lung cancer patients with EGFR gene mutations, the use of third-generation targeted drugs after early operative surgery can improve progression-free survival, but everyone is worried that postoperative adjuvant therapy will use third-generation targeted drugs.

In another study, for stage II to IIIA non-small cell lung cancer, if tumor cells have greater than 1% PD-L1 expression, then after complete resection and adjuvant chemotherapy, giving the PD-L1 inhibitor altelizumab can improve progression-free survival

What about PD-1 inhibitors? Is Pabolivizumab, referred to as K drug for adjuvant therapy for stage IB to stage IIIA non-small cell lung cancer that can be completely resected, also improve the prognosis of patients? Let's look at the following study

K drugs are used in adjuvant therapy for lung cancer

It was a randomized, double-blind, phase III clinical trial in which patients from 196 medical centers in 29 countries participated

These patients were randomly divided into two groups, with pembrolizumab intravenously given every 3 weeks at a dose of 200 mg for up to 18 cycles

From January 20, 2016 to May 6, 2020, a total of 1177 patients participated in the study, and 590 were assigned to the drug group, of which 168 patients had PD-L1 expression greater than 50%, belonging to the high-expression population
.

587 patients were on placebo, and a certain number of patients were PD-L1 highly expressed
.

As shown in the figure below, a certain proportion of patients also carry EGFR gene mutations and ALK gene mutations
.

Figure 1: The trial included a population of patients with certain driver gene mutations

The median follow-up time for this clinical trial was 35.
6 months, compared with 53.
6 months for the drug group and 42 months
for the placebo control group in the overall population.

For the population with high expression of PD-L1 (tumor cells expressing 50% of PD-L1), the median progression-free survival of the experimental and placebo groups has not yet been counted
.

High PD-L1 expression did not cause a significant difference in
the efficacy of the two groups.

Figure 2.
Disease-free survival in both groups of people

In the subgroup analysis, the second red box in the following figure is shown; Postoperative immunotherapy is better
in lung cancer patients with EGFR gene mutations.

If the patient does not use adjuvant chemotherapy after surgery, the prognosis of immunotherapy is surprisingly inferior to that of a placebo
.

The result was surprising and the reason
is unclear.

Figure 3.
Subgroup analyses containing at least 50 participants

In terms of safety, 34% of patients in the drug group treated with K drug had adverse reactions of grade 3 or above, and 26% of patients in the placebo group had adverse reactions
of grade 3 or above.

The main adverse reactions are hypertension, pneumonia, diarrhea, etc
.

Four patients died as a result of treatment-related adverse effects, mainly due to cardiogenic shock and myocarditis, septic shock and myocarditis, pneumonia, and sudden death
.

This reminds everyone of the dangers
of myocarditis.

revelation

The following conclusions were drawn from this study:

1.
Treatment with PD-1 inhibitors after surgery for early lung cancer has a longer
median progression-free survival than the placebo group.

2.
The results of subgroup analysis suggest that even if the patient's PD-L1 expression is greater than 50%, K drug can be used directly, and adjuvant chemotherapy should be used after surgery, and then treatment
with PD-1 inhibitors.

3.
For patients with EGFR gene mutations, the use of PD-1 inhibitors after surgery is better
than that of groups without EGFR gene mutations.

Of course, this conclusion needs to be verified
by more extensive research data.

One of the treatment ideas given to us by this study is to adjuvant chemotherapy directly after surgery, followed by adjuvant therapy
with PD-1 inhibitors.

Later, if it recurs, a third-generation targeted drug
is used.

I hope that this research can give you enough inspiration, more diagnosis and treatment problems welcome to join the cancer medical consultation, into the patient group exchange
.

Every day when cancer is not completely overcome, cancer is with you to spend it!

Reference: Mary O'Brien, L.
et al.
, Pembrolizumab versus placebo as adjuvant therapy for completely resected stage IB–IIIA non-small-cell lung cancer (PEARLS/KEYNOTE-091): an interim analysis of a randomised, triple-blind, phase 3 trial.
Lancet Oncol.
2022 Sep 9;

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