Abstract B049: Hyperprogressive disease after two cycles of immunotherapy in HER-2 positive metastatic gastric cancer
Notice bibliographique
Résumé
Abstract Background: Recent advancements in immune checkpoint inhibitors (ICIs) have revolutionized treatment options in many solid cancers. Pembrolizumab and nivolumab, an anti-programmed death ligand 1 (anti PD-L1) agent, has approved in treatment of advanced or metastatic gastric cancer previously treated with two or more therapies. Although immunotherapy has shown durable response in selective patients, there are also growing evidences of hyperprogression (HPD) in a subset of patients treated with ICIs. Here, we report a patient who hyper-progressed after two cycles of pembrolizumab containing regimen. Methods: Based on Response Evaluation Criteria in Solid Tumors (RECIST) 1.1, HPD is defined as time to treatment failure (TTF) <2 months and minimum increase of measurable lesions of 10mm plus one of the following: 1) increase of >40% of target lesion compared with baseline or 2) increase of >20% and appearance of multiple new lesions. Medical records of the patient were retrieved from electronic medical record (EMR). Tumor samples were obtained from stomach and liver before and after anti-PD1 treatment. Serial blood was collected to evaluate circulating tumor cells (CTC), targeted NGS of circulating free DNA (cfDNA) and immune phenotyping to identify possible underlying mechanism. To identify the mechanisms of HPD, Next-Generation Sequencing (NSG) of tissue and cfDNA of FoundationOne Liquid was utilized to analyze genomic alterations such as copy number alterations, rearrangements somatic mutations. Results: The 57 year old female, was initially diagnosed with HER2 positive advanced gastric cancer (AGC) with multiple liver metastases. Before treatment, immunohistochemistry (IHC) from stomach revealed amplification of human epidermal growth factor receptor 2 (HER2, ERbB2) with combined positive score (CPS) of 10% using PD-L1 IHC 22C3 pharmDx. She was then enrolled in the currently ongoing, investigator-initiated PANTHERA trial (NCT02901301), a phase Ib/II study of first line pembrolizumab in combination with trastuzumab, capecitabine and cisplatin. However, rapid progression was noted after two cycles. Target lesions increased by 27.1%, and several new liver metastasis as well as non-targetable lesions such as stomach and peritoneal seeding, increased. Tumor markers including CA 72-4, CA 125 and aFP also increased. Since the patient’s condition deteriorated rapidly, she was immediately started with a different chemotherapy and response evaluation with immune-related Response Evaluation Criteria in Solid Tumors (irRECIST) was not evaluated. IHC of re-biopsied stomach revealed that CPS was 30%. Notably, there were no differences in IHC of liver before and after treatment, which were both HER2 and CPS negative. Interestingly, baseline cfDNA analysis showed the amplification of EGFR, which were known to be related to HPD. Also, high level of TP53, APC mutations and Rb amplification were observed. CTC (EpCAM+CK+CD45) was initially 2 at baseline and increased to 7 after hyperprogression. Conclusion: Among 41 patients enrolled in ongoing PANTHERA trial, only one patient progressed after 2 cycles of treatment . To our knowledge, this is the first documented hyperprogression in advanced or metastatic gastric cancer after treatment with pembrolizumab. Although mechanisms behind HPD remain to be elucidated, the discrepancy in pre and post IHC results points out that tumor heterogeneity may play a role. NGS results and immune phenotyping results are pending. Citation Format: Jii Bum Lee, Garden Lee, Woo Sun Kwon, Jun Hyeok Heo, Seung-Hyun Jung, Yeun-Jun Chung, Beodul Kang, Hyo Song Kim, Hyun Cheol Chung, Sun Young Rha. Hyperprogressive disease after two cycles of immunotherapy in HER-2 positive metastatic gastric cancer [abstract]. In: Proceedings of the AACR-NCI-EORTC International Conference on Molecular Targets and Cancer Therapeutics; 2019 Oct 26-30; Boston, MA. Philadelphia (PA): AACR; Mol Cancer Ther 2019;18(12 Suppl):Abstract nr B049. doi:10.1158/1535-7163.TARG-19-B049
Récupéré en direct depuis OpenAlex et désinversé. Les résumés ne sont pas conservés dans cette base de données : les index inversés représentent 8,6 Go des 9,3 Go de texte de la base, et le serveur dispose de 13 Go libres.
Comment cette classification a été obtenuedéplier
Prédiction distillée sur la base complète
Imitation des enseignantsNi prévalence calibrée, ni vérité terrain. Validation humaine à venir. Apprise à partir de 10 348 étiquettes directes de Codex et de 10 348 étiquettes directes de Gemma. Le mode candidate est l'union des têtes enseignantes seuillées; le consensus est leur intersection. Ces sorties portent le statut machine_predicted_unvalidated et ne sont ni des étiquettes humaines ni des étiquettes directes de modèles de pointe.
Scores Codex et Gemma par catégorie
| Catégorie | Codex | Gemma |
|---|---|---|
| Métarecherche | 0,000 | 0,000 |
| Méta-épidémiologie (sens strict) | 0,000 | 0,000 |
| Méta-épidémiologie (sens large) | 0,000 | 0,000 |
| Bibliométrie | 0,000 | 0,000 |
| Études des sciences et des technologies | 0,000 | 0,000 |
| Communication savante | 0,000 | 0,000 |
| Science ouverte | 0,000 | 0,000 |
| Intégrité de la recherche | 0,000 | 0,000 |
| Charge utile insuffisante (le modèle a refusé de juger) | 0,000 | 0,000 |
Scores machine (provisoires)
Les deux têtes enseignantes du modèle étudiant, lues sur ce travail. Un score ordonne la base pour la relecture; il n'affirme jamais une catégorie, et le statut de validation accompagne chaque rangée tel quel.
Scores de référence d'un modèle non mature (critères de maturité non atteints, 7 itérations). Un score ordonne; il n'affirme jamais une catégorie.
score_only:v0-immature-baseline · tel quel depuis la passe de notation : score_only signifie que le nombre peut ordonner les travaux, et qu'aucune étiquette de catégorie n'en découleClassification
machine, non validéePrédiction automatique; un appel candidat d’une seule tête enseignante, pas un consensus.
Le détail, modèle par modèle et score par score, se trouve en fin de page sous « Comment cette classification a été obtenue ».