Lao Jiang is an advanced lung adenocarcinoma patient with an 11-year history of lung cancer, who has had a single bone metastase and brain metastases when diagnosed, and after pre-radiotherapy to control local metastases, he has been taking gefitinib orally for a full 10 years since 2011. In order to receive the medicine, every 2 months to review the CT and carcinoembryonic antigen, each time he will point to his face full of rashes and ask the same question, "This medicine can not be stopped, do you want to eat it all the time?" "No doctor dares to pack a ticket and say that you can stop the drug and stop it." Therefore, he can only continue to review, receive medicines, and take medicines again and again.
In fact, this problem is also a problem that has plagued clinicians for many years, many lung cancer patients after targeted treatment, the disease control is very good, and even CT can not find the lesion at all, at this time, do you need to eat the targeted drug forever?
In recent years, a new concept has quietly emerged, and this concept is called "drug holiday"!
"Drug holiday" is simply a period of suspension after long-term use of a certain drug, which is similar to the need for a vacation for a period of time when we work. This concept was originally proposed primarily for anti-osteoporosis drugs, bisphosphonates. Because long-term use of bisphosphonate drugs will cause drug residue accumulation, affect bone reconstruction, increase the incidence of atypical fractures and mandibular necrosis and other adverse reactions, so patients with osteoporosis with low fracture risk can temporarily stop the drug and enter the drug holiday.
At the 2021 World Conference on Lung Cancer (WCLC), Professor Wu Yilong of Guangdong Provincial People's Hospital proposed the innovative concept of "drug holiday" in the treatment of lung cancer. This P49.01 study initially confirmed the feasibility of suspension of targeted therapy in patients with advanced non-small cell lung cancer with oligostastasis with EGFR/ALK mutation positivity achieved complete remission (CR) after targeted therapy and local therapy, and blood tests for small residual lesions (MRDs) were negative.
Suspension of targeted therapy, that is, entering a "drug holiday", from the entire study, this drug holiday is based on MRD monitoring. MRD, or tiny residual lesions, refers to treatment that cannot be detected by traditional imaging (including PET/CT) or laboratory methods, but the molecular abnormalities of cancer source found by liquid biopsy, MRD represents the persistence of lung cancer and the possibility of clinical progression. At present, MRD mainly detects ctDNA by using NGS (second-generation sequencing technology) by drawing blood.
Criteria for entering a drug leave:
1. Through CT, MR or PET/CT examination, no obvious measurable lesions were found;
2. MRD negative;
3. NEGATIVE CEA.
Patients on medication leave are followed up every 3 months, and if any of the above criteria are not met during the follow-up period, targeted therapy is re-targeted.
Medication leave is mainly due to two considerations: there is no additional benefit from prolonging treatment with the drug, and prolonging treatment with the drug may increase the incidence of adverse events. For patients with targeted therapy for lung cancer, another benefit of drug holidays is to prolong the time of targeted drug resistance.
Taken together, MRD plays a key role in judging drug leave, and once MRD is positive, targeted therapy is re-targeted. However, MRD also has a limitation, that is, the assessment of brain metastases is inaccurate, which is due to the presence of the blood-brain barrier and the blood-brain-spinal fluid barrier, and plasma cannot accurately reflect the specific conditions in the skull.
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