What to do if EGFR targeted drugs are resistant? Combination therapies are worth trying

The EGFR gene is the main mutant gene in lung adenocarcinoma, and about 50% of lung adenocarcinoma patients have EGFR gene-sensitive mutations

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Previously, the cancer degree has reported that the PD-L1 inhibitor attilizumab combined with the anti-angiogenesis-targeted drug bevacizumab, chemotherapy drugs pemetrexed, cisplatin, etc.

Atenilizumab is an imported immunotherapy drug, the price is relatively expensive, so can it be replaced by domestic immunotherapy drugs? Recent studies published in Lancet Oncol, an authoritative international journal, have discussed and preliminarily confirmed this possibility

Combination therapy is effective in prolonging patient survival

This is a randomized, double-blind, multicenter Phase III clinical trial of patient recruitment in 52 hospitals in China, requiring patients aged 18 to 75 years, a pathological diagnosis of locally advanced or metastatic non-small cell lung cancer, and the presence of sensitive mutations

Between 11 July 2019 and 31 July 2021, a total of 444 patients enrolled in the clinical trial

The medication was done in each group of patients as follows:

• Group A: PD-1 inhibitors sindilimab (200 mg), bevacizumab biosimilar IBI305 (15 mg per kg of body weight), pemetrexed, and cisplatin

  
  

• Group B: PD-1 inhibitors sindilimab (200 mg), pemetrexed and cisplatin

  
  

• Group C: chemotherapy alone, using only pemetrexed and cisplatin
  .
  
  

The median follow-up time of the three groups was 9.
8 months, and the results showed that the survival time of patients in group A was significantly longer than that in group
C.

PD-1 inhibitors, bevacizumab biosimilars, and chemotherapy improve progression-free survival

As shown in the figure above, the combination of the PD-1 inhibitor sindilimab and the biosimilar IBI305 of bevacizumab and chemotherapy achieved a progression-free survival of 6.
9 months, while the median progression-free survival of patients with chemotherapy drugs alone was 4.
3 months
.

Two survival curves are visibly pulled
apart.

A total of four drugs were used in the study, and the patients suffered a lot of adverse reactions
.

The most common adverse reactions are: decreased neutrophil count, decreased white blood cell count, anemia, etc
.

However, the overall difference in the probability of adverse reactions in the three groups of patients was not large
.

That is, adding PD-1 inhibitors and bevacizumab biosimilars on the basis of chemotherapy does not significantly increase adverse reactions
.

Revelation and discussion

On the question of whether the targeted drug will be resensitized after combination therapy, the answer varies from
patient to patient.

Some patients have developed disease progression, and genetic testing through puncture sampling again has found that the previous mutation in the drug resistance gene is missing, and these patients are likely to re-use the targeted drug and benefit
from it.

There are also patients whose resistance progresses because of subtype transformation, such as into small cell lung cancer, or the emergence of rarer and trickier resistance gene mutations, or re-testing to find that the drug-resistant gene mutations still exist and the gene abundance is high, so that targeted drugs cannot be revived
.

After targeted drug resistance, the longer the "no-targeted drug treatment" in later treatment, it may lead to the gradual disappearance of previously accumulated resistance gene mutations, so that patients are more
likely to benefit from re-use of targeted drugs.

Reviewing the problem of drug resistance in targeted drugs, you can focus on cancer degrees before this article
.

What is the likelihood of a "cure" for lung cancer? Thoughts from targeted drug therapy interval chemotherapy
.

When the targeted drug is just resistant, do not refuse chemotherapy because you are afraid of the adverse effects of chemotherapy
.

Patients should communicate with the attending physician in time to choose a more suitable treatment plan
according to their physical condition.

If the patient is in good physical condition when the targeted drug is just resistant, he can withstand the combination of the four drugs above, and can try to communicate with the doctor in time
.

Once the timing is missed and the physical condition deteriorates, the adverse reactions caused by the combination treatment will be unbearable, so it will really fall into a situation where
there is no medicine available.

Fighting cancer is a long and difficult process, those patients who have successfully fought cancer for five years or even ten years, the experience during which is unimaginable to ordinary people, their persistence and optimism, and the courage to fight against the disease, is the greatest help to create miracles
.

For more anti-cancer knowledge, welcome to pay attention to the cancer degree public number and download the cancer degree app!

References: Shun Lu, et al.
, Sintilimab plus bevacizumab biosimilar IBI305 and chemotherapy for patients with EGFR-mutated non-squamous non-small-cell lung cancer who progressed on EGFR tyrosine-kinase inhibitor therapy (ORIENT-31): first interim results from a randomised, double-blind, multicentre, phase 3 trial.
Lancet Oncol.
2022 Jul 28.

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