For patients with stage III lung cancer, how to choose the path of treatment
Stage III lung cancer, also known as locally advanced lung cancer. Localized means that the tumor is still confined to the chest cavity and no metastasis of distant organs has occurred. Stage III lung cancer is a critical stage in the treatment of lung cancer, patients account for 30% of all lung cancer, most of these patients are not suitable for surgical treatment, the current standard treatment is chemotherapy combined with simultaneous chest radiotherapy.
Thanks to the emergence of the PD-L1 inhibitor valliyumab as a consolidation therapy after concurrent chemoradiotherapy for locally advanced non-small cell lung cancer, the median progression-free survival of patients reached 17.2 months, and the survival rate of more than two years was 66.3%.
However, recent literature suggests that if patients with stage III non-small cell lung cancer have mutations in the EGFR gene or HER2 gene, the use of duvalliumab consolidation therapy is not very effective. Since the sample size of this conclusion is small, further research is needed.
Therefore, for patients with non-small cell lung cancer who are inoperable in stage III and have mutations in the EGFR gene, the current treatment is simultaneous chemoradiation. But what if the patient is physically ill and cannot receive chemotherapy?
How to give this part of the patients a chance to cure through more effective treatment measures is the direction that researchers have been working on. Therefore, there are constantly new research reports around this type of lung cancer.
Currently, for patients with stage III lung cancer with an inoperable EGFR gene mutation, the vast majority of experts recommend targeted drug therapy, and do not recommend the use of valliyumab consolidation therapy after radiotherapy and chemotherapy in these patients.
Since patients with EGFR mutations who can be operated on can be treated with targeted drugs, can we consider using targeted drug therapy for this part of the patients who are not inoperable? The study that Cancer Degrees share with you today confirms the efficacy of radiotherapy combined with targeted therapy.
Patients with non-surgical EGFR mutations:
Gefitinib combined with chest radiotherapy has a significant effect
This is a single-arm Phase II clinical trial in which patients are stage III unresectable non-small cell lung adenocarcinoma with sensitive mutations in the EGFR gene (exon 19 deletion mutation or L858R point mutation). Among them, patients over 75 years of age with lymph node metastases, lung metastases, or atelectasis on the contralateral hilars were not included in this clinical trial.
These patients took gefitinib 250 mg orally daily for two consecutive years while receiving radiation therapy to the chest. Radiation therapy begins on the first day of taking the targeted drug, 5 days a week, in a dose of 2 Gy per day, with a total radiation dose of 64 Gy.
Figure 1: Overall treatment of patients in clinical trials
Between August 2012 and November 2017, a total of 28 patients were enrolled, one of whom was excluded for reasons of informed consent. Patients undergo CT scans every two months to assess the progression of the tumor. The median follow-up time for the entire group of patients was 51.8 months.
Although the study designed the drug for a two-year duration, the median time for patients to actually administer the drug was 332 days. Six of the 27 patients completed treatment set out in the study, and another 21 discontinued treatment due to pneumonia and disease progression.
Research data shows that:
The median progression-free survival time of enrolled patients was 18.6 months, with 66.7% of diseases progressing within one year and 33.3% of diseases within two years.
2. All visible lesions disappeared in 3 patients and achieved complete clinical remission; 19 patients had tumor lesions shrink by more than 30%, achieving clinical partial remission. The response rate for overall treatment was 81.5%.
3. The median total survival time for all enrolled patients was 61.1 months.
Figure 2. Median progression-free survival for all patients
Figure 3. Median overall survival of patients
Treatment-related adverse effects were pneumonia (the median time from the start of treatment to the onset of pneumonia was 92 days), elevated alanine aminotransferase, and elevated aspartate aminotransferase. Most treatment-related adverse effects were grade 1 to 2, with no treatment-related deaths.
Of the 8 patients who discontinued treatment for pneumonia, 4 resumed medication after the pneumonia remission. The median progression-free survival of these 8 patients was 13.7 months, which was much shorter than the progression-free survival of the overall population. Since most patients' pneumonia occurred after chest radiotherapy, two patients did not complete chest radiotherapy, their overall radiation dose was 38 Gy and 50 Gy, and the progression-free survival was 17 months and 70.7 months, respectively.
In addition, data analysis on recurrence of the condition showed:
1. 22 out of 27 patients experienced a recurrence.
2. There are 25 recurrence sites, most of which are outside the radiation therapy area.
3. The appearance of new metastases in the brain is the most common situation, with 10 patients developing brain metastases, most of which occur after one year of gefitinib treatment.
4. After stereotactic radiation therapy in patients with brain metastases, there was no particular improvement in progression-free survival, but overall survival seemed to be better than in patients with relapses at other sites.
revelation
This study answers the question of maintenance therapy for patients with stage III lung cancer with mutations in the EGFR gene. These patients carry mutations in the EGFR gene, and the efficacy of the immunotherapy drug duvalliumab is not well understood.
However, through the combination of the targeted drug gefitinib and chest radiotherapy, the patient achieved a relatively good survival benefit, and more importantly, the patient's quality of life was also improved by replacing chemotherapy with gefitinib.
Of course, the number of patients enrolled in this study is relatively small, and the conclusions need to be further verified. In addition, if gefitinib is replaced by erlotinib or osimertinib, will the patient's survival benefit be better? I believe that these problems will have corresponding research reports in the future.
参考文献：Akamatsu H, et al., Gefitinib with concurrent thoracic radiotherapy in unresectable locally advanced non-small cell lung cancer with EGFR mutation; West Japan Oncology Group 6911L, Journal of Thoracic Oncology (2021)
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