Phase III KEYNOTE-590 study of chemotherapy + pembrolizumab versus chemotherapy + placebo as first-line therapy for patients (Pts) with advanced esophageal or esophagogastric junction (E/EGJ) cancer

Kato, Ken; Shah, Manish A.; Enzinger, Peter C.; Bennouna, Jaafar; Shen, Lin; Adenis, Antoine; Sun, Joo Sung; Cho, B.C.; Özgüroǧlu, Mustafa; Kojima, Takashi; Kostorov, V.; Hierro, Cinta; Zhu, Ying; Shah, Supriya; Bhagia, Pooja; Doi, Toshihiko

doi:10.1093/annonc/mdy282.168

Cited by 9 publications

(13 citation statements)

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“…Unsatisfactory immune monotherapies in gastric cancer make combined therapy especially enticing. Although, most of the combination strategies being investigated in gastric cancer are in the preclinical or early clinical research stage, few have entered the phase III stage [112]. For example, the CheckMate-649 is further assessing the difference in survival between nivolumab plus ipilimumab and chemotherapy although results are pending.…”

Section: Current Applications Of Combination Immunotherapy In Gastroimentioning

confidence: 99%

Combination regimens with PD-1/PD-L1 immune checkpoint inhibitors for gastrointestinal malignancies

Wang

Lin

et al. 2019

J Hematol Oncol

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Gastrointestinal (GI) malignant neoplasms have a high global incidence and treatment prospects for patients with advanced GI tumors are dismal. PD-1/PD-L1 inhibitors emerged as a frontline treatment for several types of cancer. However, the shortcomings of PD-1/PD-L1 inhibitors have been observed, including low objective response rates and acquired tumor resistance, especially in patients receiving PD-1/PD-L1 inhibitors as a single treatment. Accumulating evidence from clinical trials increasingly suggests that combined immunotherapies enhance therapeutic responses in patients with malignances, especially for GI tumors which have a complex matrix, and significant molecular and immunological differences. Preclinical and clinical studies suggest there are advantages to combined immunological regimens, which represents the next logical step in this field, although further research is necessary. This literature review explores the current limitations of monotherapies, before critically discussing the rationale behind combination regimens. Then, we provide a summary of the clinical applications for gastrointestinal cancers.

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Section: Current Applications Of Combination Immunotherapy In Gastroimentioning

confidence: 99%

Combination regimens with PD-1/PD-L1 immune checkpoint inhibitors for gastrointestinal malignancies

Wang

Lin

et al. 2019

J Hematol Oncol

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“…The combination of PD-1/PD-L1 inhibitors with systemic chemotherapy has achieved success in the treatment of various solid tumors, including nonsmall cell lung cancer, extensive stage small cell cancer and esophageal cancer. [16][17][18] Oxaliplatin, the third-generation platinum agent, in combination with gemcitabine has demonstrated similar efficacy to the GP regimen as first-line treatment for advanced BTC. 19,20 In recent years, accumulating evidence suggests that the antitumor activity of oxaliplatin differed from cisplatin, with its immunological effects.…”

Section: Introductionmentioning

confidence: 99%

“…Combination immunotherapy is a common approach to further improve immune response. The combination of PD‐1/PD‐L1 inhibitors with systemic chemotherapy has achieved success in the treatment of various solid tumors, including nonsmall cell lung cancer, extensive stage small cell cancer and esophageal cancer 16‐18 . Oxaliplatin, the third‐generation platinum agent, in combination with gemcitabine has demonstrated similar efficacy to the GP regimen as first‐line treatment for advanced BTC 19,20 .…”

Section: Introductionmentioning

confidence: 99%

Camrelizumab plus oxaliplatin‐based chemotherapy as first‐line therapy for advanced biliary tract cancer: A multicenter, phase 2 trial

Chen

Qin

et al. 2021

Intl Journal of Cancer

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Biliary tract cancer (BTC) is a highly malignant tumor with limited treatment options and poor prognosis. Our study aimed to evaluate camrelizumab plus oxaliplatin-based chemotherapy as first-line therapy for advanced BTC. In this multicenter, open-label, phase 2 trial conducted in China (ClinicalTrials.gov, NCT03092895), untreated patients with advanced BTC were given camrelizumab (3 mg/kg iv drip injection, every 2 weeks) plus typical FOLFOX4 (Cam-FOLFOX4 group; infusional 5-fluorouracil, leucovorin and oxaliplatin) or GEMOX (Cam-GEMOX group; infusional gemcitabine and oxaliplatin). The primary endpoint was objective response rate (ORR). Ninety-two patients were enrolled: 29 received Cam-FOLFOX4 and 63 received Cam-GEMOX. The confirmed ORR and disease control rate were 16.3% (95% confidence interval [CI] = 9.4-25.5) and 75.0% (95% CI = 64.9-83.4), respectively. Median duration of response was 8.7 months (95% CI = 5.1-not reached).Median progression-free survival and overall survival were 5.3 months (95% CI = 3.7-5.7) and 12.4 months (95% CI = 8.9-16.1), respectively. Grade ≥3 treatment-related adverse events (TRAEs) occurred in 82.8% of patients receiving Cam-FOLFOX4 and in 68.3% receiving Cam-GEMOX, with no unexpected effects observed. Six (6.5%) patients discontinued treatment due to TRAE.

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“…Despite this limitation, patients who received first-, second-, or third-line EGFRi exceeded the objective response rate, PFS, and OS reported in contemporary studies, respectively. [2][3][4][5]37 Of note, many patients developed oligometastatic progression after initial treatment response yet went on to have extended OS. This presumably reflects intrapatient heterogeneity, and in many cases, this was driven by co-occurring HER2 expression, with the receipt of subsequent HER2-directed therapies.…”

Section: Discussionmentioning

confidence: 99%

Epidermal Growth Factor Receptor Inhibition in Epidermal Growth Factor Receptor–Amplified Gastroesophageal Cancer: Retrospective Global Experience

Maron

Moya

Morano

et al. 2022

JCO

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PURPOSE Subset analyses from phase III evaluation of epidermal growth factor receptor inhibition (EGFRi) suggest improved outcomes in patients with EGFR-amplified gastroesophageal adenocarcinoma (GEA), but large-scale analyses are lacking. This multi-institutional analysis sought to determine the role of EGFRi in the largest cohort of patients with EGFR-amplified GEA to date. PATIENTS AND METHODS A total of 60 patients from 15 tertiary cancer centers in six countries met the inclusion criteria. These criteria required histologically confirmed GEA in the metastatic or unresectable setting with EGFR amplification identified by using a Clinical Laboratory Improvement Amendments–approved assay, and who received on- or off-protocol EGFRi. Testing could be by tissue next-generation sequencing, plasma circulating tumor DNA next-generation sequencing, and/or fluorescence in situ hybridization performed by a Clinical Laboratory Improvement Amendments approved laboratory. Treatment patterns and outcomes analysis was also performed using a deidentified clinicogenomic database (CGDB). RESULTS Sixty patients with EGFR-amplified GEA received EGFRi, including 31 of 60 patients (52%) with concurrent chemotherapy. Across treatment lines, patients achieved a 43% objective response rate with a median progression-free survival of 4.6 months (95% CI, 3.5 to 6.4). Patients receiving EGFRi in first-, second-, and third-line therapy achieved a median overall survival of 20.6 months (95% CI, 13.5 to not reached [NR]), 9 months (95% CI, 7.9 to NR), and 8.4 months (7.6 to NR), respectively. This survival far exceeded the 11.2-month (95% CI, 8.7 to 14.2) median overall survival from first-line initiation of non-EGFRi therapy in patients with EGFR-amplified GEA in the CGDB. Despite this benefit, analysis of the CGDB (January 2011-December 2020) suggests that only 5% of patients with EGFR-amplified GEA received EGFRi. CONCLUSION Patients with EGFR-amplified GEA derive significant benefit from EGFRi. Further prospective investigation of EGFRi in a well-selected patient population is ongoing in an upcoming trial of amivantamab in EGFR and/or MET amplified GEA.

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Phase III KEYNOTE-590 study of chemotherapy + pembrolizumab versus chemotherapy + placebo as first-line therapy for patients (Pts) with advanced esophageal or esophagogastric junction (E/EGJ) cancer

Cited by 9 publications

References 0 publications

Combination regimens with PD-1/PD-L1 immune checkpoint inhibitors for gastrointestinal malignancies

Combination regimens with PD-1/PD-L1 immune checkpoint inhibitors for gastrointestinal malignancies

Camrelizumab plus oxaliplatin‐based chemotherapy as first‐line therapy for advanced biliary tract cancer: A multicenter, phase 2 trial

Epidermal Growth Factor Receptor Inhibition in Epidermal Growth Factor Receptor–Amplified Gastroesophageal Cancer: Retrospective Global Experience

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