Genomic correlates of response and resistance to immune checkpoint inhibitors in carcinomas of unknown primary

2021 ◽  
Author(s):  
Elie Rassy ◽  
Stergios Boussios ◽  
Nicholas Pavlidis
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Unknown Primary

scholarly journals Biologic subtypes of melanoma predict survival benefit of combination anti-PD1+anti-CTLA4 immune checkpoint inhibitors versus anti-PD1 monotherapy

2021 ◽  
Vol 9 (1) ◽  
pp. e001642
Author(s):  
April A N Rose ◽  
Susan M Armstrong ◽  
David Hogg ◽  
Marcus O Butler ◽  
Samuel D Saibil ◽  
...  
Keyword(s):  
Metastatic Melanoma ◽  
Immune Checkpoint ◽  
Primary Tumor ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Advanced Melanoma ◽  
Unknown Primary ◽  
Tumor Type ◽  
Multivariable Analyses ◽  
Primary Tumor Type

PurposeAnti-programmed cell death protein 1 (PD1)±anti-cytotoxic T-lymphocyte associated protein 4 (CTLA4) immune checkpoint inhibitors (ICIs) are standard therapeutic options for metastatic melanoma. We assessed whether biologic subtype according to primary tumor type or genomic subtype can function as predictive biomarkers for anti-PD1±anti-CTLA4 ICI in patients with advanced melanoma.MethodsWe performed a single-center retrospective cohort analysis of patients who received anti-PD1±anti-CTLA4 ICI for advanced melanoma between 2012 and 2019. Primary tumor type, BRAF and NRAS mutation status, and other covariates were abstracted from chart review. Log-rank tests and multivariable Cox regression models were used to assess differences in clinical progression-free (cPFS) and overall survival (OS).ResultsWe identified 230 patients who received 249 lines of anti-PD1±anti-CTLA4 ICI for unresectable or metastatic disease. Of these patients, 74% were cutaneous, 11% mucosal, 8% unknown primary and 7% acral. BRAF and NRAS mutations were identified in 35% and 28% of patients, respectively. In multivariable analyses of the entire cohort, acral or mucosal primary tumor type, >3 metastatic sites, elevated LDH were predictive of shorter cPFS and OS. Combination ICI therapy was associated with longer cPFS (HR 0.57, 95% CI 0.38 to 0.86, p=0.007) and OS (HR 0.42, 95% CI 0.28 to 0.65, p<0.001). Combination ICI was significantly associated with longer OS in unknown primary and mucosal melanoma. There was a non-significant trend toward longer OS with anti-PD1+anti-CTLA4 in cutaneous melanoma, but not in acral melanoma. In multivariable analyses, combination ICI was associated with longer OS in NRAS (HR 0.24, 95% CI 0.10 to 0.62, p=0.003, n=69) and BRAF V600E/K (HR 0.47, 95% CI 0.24 to 0.90, p=0.024, n=86) mutant melanoma but not BRAF/NRAS wild-type (n=94) melanoma.ConclusionsIn our cohort, primary melanoma tumor type and genomic subtype were independent predictive markers of cPFS and OS for patients with metastatic melanoma receiving anti-PD1 ICI. Primary tumor type and genomic subtype—including NRAS—should be further evaluated in prospective clinical trials to determine their value as predictive markers. Biologic subtypes may facilitate clinical decision-making when recommending combination ICI treatment (anti-PD1±anti-CTLA4) versus anti-PD1 alone for patients with metastatic melanoma.

scholarly journals Immune checkpoint inhibitors: Real-world experience from India in advanced solid cancers that have progressed on chemotherapy

2019 ◽  
Vol 08 (01) ◽  
pp. 65-68 ◽  
Author(s):  
Vineet Govinda Gupta ◽  
Ranga Rao Rangaraju ◽  
Waseem Abbas ◽  
Peush Bajpai ◽  
Ruchika Khetrapal
Keyword(s):  
Real World ◽  
Immune Checkpoint ◽  
Clinical Benefit ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Case Reports ◽  
Progression Free Survival ◽  
Unknown Primary ◽  
International Studies ◽  
Real World Data

Abstract Context: The immune checkpoint inhibitors (ICIs) nivolumab and pembrolizumab have shown dramatic efficacy with low toxicity in international studies of advanced solid cancers. No published Indian experience with ICIs exist other than isolated case reports. Aims: The aim of this study is to evaluate real-world data about the efficacy and toxicity of ICIs in advanced solid cancers among Indian patients who have progressed on one or more prior lines of chemotherapy. Materials and Methods: All patients with advanced solid cancers who received ICIs after the failure of chemotherapy at our center were retrospectively assessed. Information about efficacy and toxicity was collected and analyzed. Results: The present study included 24 patients who had received ICIs for indications including non-small cell lung, bladder, head and neck, gastrointestinal, and unknown primary cancer. Patients had received a median of two prior lines of chemotherapy (range 1–5). Grade III or higher toxicity was seen in 8% of patients. Clinical benefit at 3 months was realized in 33% of evaluable patients. Twenty-six percentages of evaluable patients achieved a response, including one patient who achieved a complete response that is ongoing at 18 months. Median progression-free survival was 3 months, and median overall survival was 8 months at a median follow-up of 10 months. Among patients who achieved clinical benefit, the majority (84%) have an ongoing response at the time of data cutoff. Conclusions: Efficacy and toxicity of ICIs in the Indian population are similar to the experience seen in large international cohorts, and Indian oncologists may feel reassured using these agents in similar settings.

Abstract #827: Panhypopituitarism Due to Immune Checkpoint Inhibitors

2017 ◽  
Vol 23 ◽  
pp. 176-177
Author(s):  
Kaitlyn Steffensmeier ◽  
Bahar Cheema ◽  
Ankur Gupta
Keyword(s):  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors

A Case of Malignant Melanoma Associated with Polymyositis Treated with Immune Checkpoint Inhibitors

2019 ◽  
Vol 81 (5) ◽  
pp. 396-400 ◽  
Author(s):  
Hayato NOMURA ◽  
Osamu YAMASAKI ◽  
Tatsuya KAJI ◽  
Hiroshi WAKABAYASHI ◽  
Yoshia MIYAWAKI ◽  
...  
Keyword(s):  
Malignant Melanoma ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors

Immune checkpoint and checkpoint inhibitors in hepatocellular carcinoma

2018 ◽  
Vol 1 (1) ◽  
pp. 28-32
Author(s):  
Piyawat Komolmit
Keyword(s):  
Hepatocellular Carcinoma ◽  
T Cells ◽  
Major Histocompatibility Complex ◽  
T Cell Receptor ◽  
Immune Checkpoint ◽  
Immune Checkpoint Inhibitors ◽  
Checkpoint Inhibitors ◽  
Cell Receptor ◽  
Immune Checkpoints ◽  
Histocompatibility Complex

การรักษามะเร็งด้วยแนวความคิดของการกระตุ้นให้ภูมิต้านทานของร่างกายไปทำลายเซลล์มะเร็งนั้น ปัจจุบันได้รับการพิสูจน์ชัดว่าวิธีการนี้สามารถหยุดยั้งการแพร่กระจายของเซลล์มะเร็ง โดยไม่ก่อให้เกิดภาวะแทรกซ้อนทางปฏิกิริยาภูมิต้านทานต่ออวัยวะส่วนอื่นที่รุนแรง สามารถนำมาใช้ทางคลินิกได้ ยุคของการรักษามะเร็งกำลังเปลี่ยนจากยุคของยาเคมีบำบัดเข้าสู่การรักษาด้วยภูมิต้านทาน หรือ immunotherapy ยากลุ่ม Immune checkpoint inhibitors โดยเฉพาะ PD-1 กับ CTLA-4 inhibitors จะเข้ามามีบทบาทในการรักษามะเร็งตับในระยะเวลาอันใกล้ จำเป็นแพทย์จะต้องมีความรู้ความเข้าใจในพื้นฐานของ immune checkpoints และยาที่ไปยับยั้งโมเลกุลเหล่านี้ Figure 1 เมื่อ T cells รับรู้แอนทิเจนผ่านทาง TCR/MHC จะมีปฏิกิริยาระหว่าง co-receptors หรือ immune checkpoints กับ ligands บน APCs หรือ เซลล์มะเร็ง ทั้งแบบกระตุ้น (co-stimulation) หรือยับยั้ง (co-inhibition) TCR = T cell receptor, MHC = major histocompatibility complex

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