June 18, 2024

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Immunotherapy Breakthrough: Single Drug Reverses the Trend 

Immunotherapy Breakthrough: Single Drug Reverses the Trend 

Immunotherapy Breakthrough: Single Drug Reverses the Trend 

For non-small cell lung cancer (NSCLC) patients with negative driver gene mutations, the current clinical standard treatment strategy involves a combination of immunotherapy and chemotherapy.

In practical clinical use, the issue of hyperprogression during immunotherapy often limits the overall survival (OS) benefits for patients.

Previous studies have shown that the occurrence rate of hyperprogression (HPD) in NSCLC is 14%, and this subset of patients often experiences a significant reduction in their survival period due to a lack of options for subsequent therapies.

In June of this year, Immunotherapy published a full report on a case of NSCLC where hyperprogression occurred after third-line PD-1 treatment but was successfully reversed with a single drug, an anti-angiogenic agent. This case offers hope for potential insights into clinical interventions for individuals at risk of immunotherapy hyperprogression.


Immunotherapy Breakthrough: Single Drug Reverses the Trend 




Treatment Process and Outcome

The patient was a 55-year-old male who first sought medical attention in October 2018. He had a 40-year history of smoking, no family history of tumors or lung diseases, and was diagnosed with poorly differentiated lung cancer with extensive bone metastases three months prior.


First-Line Treatment

After receiving two cycles of docetaxel and cisplatin treatment, he experienced right adrenal gland metastasis and left lung progression. Tumor tissue biopsy guided by CT scan revealed negative driver gene mutations, making targeted therapy ineffective.


Second-Line Treatment

Following four cycles of pembrolizumab and cisplatin treatment, the patient experienced a second progression, and driver gene testing remained negative, with weak positive (5%) PD-L1 expression.


Third-Line Treatment

Considering the above findings, the patient was started on PD-1 checkpoint inhibitor therapy every three weeks. However, after two cycles, he developed worsening breathing difficulties, a significant increase in tumor markers, and a more than 50% enlargement of the left lung lesion, leading to a diagnosis of immunotherapy hyperprogression.


Treatment Strategy

Based on a comprehensive assessment of the patient’s condition, a single drug treatment plan with oral administration of a certain anti-angiogenic agent (referred to as X) was chosen. For the first 14 days of treatment, the patient took 12mg of X orally daily, followed by a 7-day drug-free interval before starting the next treatment cycle.

After just two weeks, the patient’s lung lesions ceased to progress, with CT scans showing a significant reduction in lung lesions, indicating partial relief. Subsequent treatment benefited the patient, and he was eventually discharged.

Unfortunately, seven months after starting treatment, the patient passed away due to a lung infection.

The identity of the anti-angiogenic drug X and the optimal clinical intervention and management strategies for immunotherapy hyperprogression remain subjects of investigation.

For more details, please refer to the cited research articles [1] and [2].




Immunotherapy Breakthrough: Single Drug Reverses the Trend 


[1]Lu Chen et al, Anlotinib succeeded in rescue therapy for hyperprogression induced by immune checkpoint inhibitors: a case report, Immunotherapy (2023).

[2]Li G, Choi JE, Kryczek I, Sun Y, Liao P, Li S, Wei S, Grove S, Vatan L, Nelson R, Schaefer G, Allen SG, Sankar K, Fecher LA, Mendiratta-Lala M, Frankel TL, Qin A, Waninger JJ, Tezel A, Alva A, Lao CD, Ramnath N, Cieslik M, Harms PW, Green MD, Chinnaiyan AM, Zou W. Intersection of immune and oncometabolic pathways drives cancer hyperprogression during immunotherapy. Cancer Cell. 2023 Feb 13;41(2):304-322.e7. doi: 10.1016/j.ccell.2022.12.008. Epub 2023 Jan 12. PMID: 36638784; PMCID: PMC10286807.

(source:internet, reference only)

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