57O Efficacy, safety and tolerability of MEDI4736 (durvalumab [D]), a human IgG1 anti-programmed cell death-ligand-1 (PD-L1) antibody, combined with gefitinib (G): A phase I expansion in TKI-naïve patients (pts) with EGFR mutant NSCLC

Gibbons, Don L.; Chow, Laura Q.M.; Kim, D. W.; Kim, S. W.; Yeh, Tammie C.; Song, Xuyang; Jiang, Haiyi; Taylor, Rosie; Karakunnel, Joyson; Creelan, Ben

doi:10.1016/s1556-0864(16)30171-x

Cited by 119 publications

(80 citation statements)

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“…On the other hand, Ahn et al (9) reported that ILD was observed in 38% of cases receiving combination treatment with osimertinib and durvalumab, a PD-L1 inhibitor, which suggests that treatment with such a drug combination may dramatically increase the risk of ILD. Notably, a similar increased risk of ILD has not been reported for combination treatment with durvalumab and gefitinib (10). These studies suggest that previous treatment with nivolumab may affect the onset of ILD during osimertinib treatment.…”

Section: Discussionsupporting

confidence: 63%

Osimertinib-induced interstitial lung disease in a patient with non-small cell lung cancer pretreated with nivolumab: A case report

Takakuwa

Oguri

Uemura

et al. 2017

Molecular and Clinical Oncology

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Abstract. Osimertinib (AZD9291) is a third-generation epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor approved for EGFR-T790M-positive non-small cell lung cancer. A high incidence of interstitial lung disease (ILD) during combination treatment with osimertinib and anti-programmed cell death-ligand 1 (PD-L1) inhibitor has been reported. The current study presents a case of ILD development during osimertinib treatment following nivolumab (an anti-PD-1 antibody) treatment. The 59-year-old female was diagnosed with stage IV lung adenocarcinoma harboring a deletion in exon 19 of the EGFR gene. Following nivolumab as a sixth-line treatment, an EGFR-T790M-encoding mutation in EGFR exon 20 was identified by re-biopsy. Osimertinib was therefore initiated as a seventh-line treatment. A partial response was subsequently noted; however, 63 days after initiation of the treatment the patient presented with dyspnea with decreased oxygenation in the absence of fever and sputum. A computed tomography scan revealed the emergence of ground-glass opacities with bronchiectasis in both lungs, and a diagnosis of ILD due to osimertinib was made. Following steroid pulse therapy with discontinuation of osimertinib, the patient's chest findings and respiratory condition improved. Therefore, it is considered that anti-PD-1 therapies may be associated with a risk of ILD during subsequent osimertinib treatment. IntroductionThe discovery of epidermal growth factor receptor (EGFR)-acti vating mutations in non-small cell lung cancer (NSCLC) and EGFR tyrosine kinase inhibitors (TKIs) have changed the strategy of NSCLC therapy. Recently, EGFR-TKIs, including gefitinib, erlotinib and afatinib, have become the standard therapy for patients with advanced EGFR-mutated NSCLC. However, the majority of the patients progress and second-line therapy is required.The EGFR T790M point mutation (T790M) is the most common mechanism underlying drug resistance to EGFR-TKIs in EGFR mutation-positive NSCLC patients. Osimertinib (AZD9291) is a third-generation EGFR-TKI approved for the treatment of EGFR-T790M-positive NSCLC (1). Furthermore, immune checkpoint modulation with programmed death-1 (PD-1) or programmed death-ligand 1 (PD-L1) inhibition has also shown promise in changing the strategy of NSCLC therapy. Nivolumab, an anti-PD-1 inhibitor, is a novel drug used in the second-line treatment of NSCLC (2). In both EGFR-TKI and immune checkpoint inhibitors therapy, interstitial lung disease (ILD) is recognized as one of most severe adverse events. These two therapies may be sequentially applied in the same patient, but the effects of the interaction between these two drugs on the risk of ILD remains unclear. A case of ILD that occurred during osimertinib treatment in a patient with a history of previous nivolumab treatment is reported herein. Case reportA 59-year-old female was diagnosed with stage IV (cT3N2M1a) lung adenocarcinoma harboring a deletion in exon 19 of the EGFR gene. The patient was treated with platinum-pemetrexed with bevacizumab...

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Section: Discussionsupporting

confidence: 63%

Osimertinib-induced interstitial lung disease in a patient with non-small cell lung cancer pretreated with nivolumab: A case report

Takakuwa

Oguri

Uemura

et al. 2017

Molecular and Clinical Oncology

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“…gov number NCT02454933) evaluating the combination of durvalumab with osimertinib compared to osimertinib alone in patients with T790M positive NSCLC following a prior EGFR TKI has been also suspended. Similarly to the TATTON study, another phase I open-label multicenter study (ClinicalTrials.gov number NCT02088112) was initiated to evaluate durvalumab in combination with gefitinib as first line therapy in EGFR mutant NSCLC and the expansion phase data have been reported (34). No clinically relevant differences in the objective response rate (79%) compared to what is already known for gefitinib monotherapy (73.7%) (55) in this setting were observed ( Table 2).…”

Section: Introductionmentioning

confidence: 97%

“…No clinically relevant differences in the objective response rate (79%) compared to what is already known for gefitinib monotherapy (73.7%) (55) in this setting were observed ( Table 2). Overall 55% of the patients suffered grade 3 adverse events and treatment discontinuation due to adverse events was reported in 20% of the patients (34).…”

Section: Introductionmentioning

confidence: 99%

The combination of checkpoint immunotherapy and targeted therapy in cancer

Karachaliou¹,

Cao²,

Sosa³

et al. 2017

Ann. Transl. Med.

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Abstract:The therapeutic possibilities for patients with metastatic melanoma have changed due to the development of targeted therapies that inhibit oncogenic signaling pathways as well as immune modulating therapies that unleash the patient antitumor immunity. These therapeutic changes have impressively increased the median overall survival of the patients. Considering the dramatic but transient responses that occur with targeted therapies for a subgroup of patients and the durable responses that can be achieved with immunotherapy in a subset of patients, a lot of effort is ongoing for the clinical development of combinations of these two therapeutic approaches. Herein we discuss the existing preclinical and clinical data for the combination of targeted therapies and immunotherapy focusing mainly on melanoma and non-small cell lung cancer (NSCLC).

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“…High rates of grade 3/4 treatment related toxicity (55%) was also reported in a phase I study of durvalumab and gefitinib (18). The combination of erlotinib with atezolizumab reported an ORR of 75% and disease control rate of 95%, with 39% grade 3/4 adverse events (19).…”

mentioning

confidence: 65%

The KEY to the end of chemotherapy in non-small cell lung cancer?

Huang

Soo

2017

Annals of Translational Medicine

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57O Efficacy, safety and tolerability of MEDI4736 (durvalumab [D]), a human IgG1 anti-programmed cell death-ligand-1 (PD-L1) antibody, combined with gefitinib (G): A phase I expansion in TKI-naïve patients (pts) with EGFR mutant NSCLC

Abstract: Translational research 57O Efficacy, safety and tolerability of MEDI4736 (durvalumab [D]), a human IgG1 antiprogrammed cell death-ligand-1 (PD-L1) antibody, combined with gefitinib (G): A phase I expansion in TKI-naïve patients (pts) with EGFR mutant NSCLC

Cited by 119 publications

References 0 publications

Osimertinib-induced interstitial lung disease in a patient with non-small cell lung cancer pretreated with nivolumab: A case report

Osimertinib-induced interstitial lung disease in a patient with non-small cell lung cancer pretreated with nivolumab: A case report

The combination of checkpoint immunotherapy and targeted therapy in cancer

The KEY to the end of chemotherapy in non-small cell lung cancer?

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