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AstraZeneca Provides Update on the Phase III MYSTIC Trial of Imfinzi and Tremelimumab in Stage IV Non-Small Cell Lung Cancer

(AstraZeneca) Nov 16, 2018 - AstraZeneca and MedImmune, its global biologics research and development arm, today announced final overall survival (OS) results for the Phase III MYSTIC trial, a randomised, open-label, multi-centre, global trial of Imfinzi (durvalumab) monotherapy and the combination of Imfinzi and tremelimumab, an anti-CTLA4 antibody, versus standard-of-care (SoC) platinum-based chemotherapy in previously-untreated patients with Stage IV (metastatic) non-small cell lung cancer (NSCLC). In the primary analysis population of patients, whose tumours express PD-L1 on 25% or more of their cancer cells as determined by the VENTANA PD-L1 (SP263) Assay, Imfinzi monotherapy and the combination of Imfinzi plus tremelimumab did not meet the primary endpoints of improving OS compared to SoC chemotherapy. While the OS result did not meet statistical significance, a hazard ratio (HR) of 0.76 (97.54% CI 0.564-1.019; nominal p=0.036) was observed with Imfinzi monotherapy. The combination therapy had an HR of 0.85 (98.77% CI 0.611-1.173; nominal p=0.202); the data support further analysis in exploratory subgroups.

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H. Jack West, MD (Posted: November 16, 2018)

quotesI think there are a few key findings. First, obviously nothing here changes our standard of care in advanced NSCLC. Second, the durvalumab arm was statistically negative but had a hazard ratio for OS of 0.76, negative just due to prior alpha spending. These results don't supplant pembro in first line NSCLC, but don't represent a true failure of durvalumab that should lead us to question using it in a setting like stage III NSCLC, where consolidation durvalumab was highly positive for a PFS & OS benefit on the PACIFIC trial. Third, the durva/treme arm looked worse. This may be due to toxicity limiting ability to treat. Regardless, I think we should have very little enthusiasm for this combination. We will need to see whether nivolumab/ipilimumab suffers the same date and whether selection by tumor mutational burden in IO combinations pans out.quotes

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AstraZeneca Provides Update on the Phase III MYSTIC Trial of Imfinzi and Tremelimumab in Stage IV Non-Small Cell Lung Cancer

(AstraZeneca) Nov 16, 2018 - AstraZeneca and MedImmune, its global biologics research and development arm, today announced final overall survival (OS) results for the Phase III MYSTIC trial, a randomised, open-label, multi-centre, global trial of Imfinzi (durvalumab) monotherapy and the combination of Imfinzi and tremelimumab, an anti-CTLA4 antibody, versus standard-of-care (SoC) platinum-based chemotherapy in previously-untreated patients with Stage IV (metastatic) non-small cell lung cancer (NSCLC). In the primary analysis population of patients, whose tumours express PD-L1 on 25% or more of their cancer cells as determined by the VENTANA PD-L1 (SP263) Assay, Imfinzi monotherapy and the combination of Imfinzi plus tremelimumab did not meet the primary endpoints of improving OS compared to SoC chemotherapy. While the OS result did not meet statistical significance, a hazard ratio (HR) of 0.76 (97.54% CI 0.564-1.019; nominal p=0.036) was observed with Imfinzi monotherapy. The combination therapy had an HR of 0.85 (98.77% CI 0.611-1.173; nominal p=0.202); the data support further analysis in exploratory subgroups.

Read Article arrow

H. Jack West, MD (Posted: November 16, 2018)

quotesI think there are a few key findings. First, obviously nothing here changes our standard of care in advanced NSCLC. Second, the durvalumab arm was statistically negative but had a hazard ratio for OS of 0.76, negative just due to prior alpha spending. These results don't supplant pembro in first line NSCLC, but don't represent a true failure of durvalumab that should lead us to question using it in a setting like stage III NSCLC, where consolidation durvalumab was highly positive for a PFS & OS benefit on the PACIFIC trial. Third, the durva/treme arm looked worse. This may be due to toxicity limiting ability to treat. Regardless, I think we should have very little enthusiasm for this combination. We will need to see whether nivolumab/ipilimumab suffers the same date and whether selection by tumor mutational burden in IO combinations pans out.quotes

Add Comment 3 Comment
forumImage

AstraZeneca Provides Update on the Phase III MYSTIC Trial of Imfinzi and Tremelimumab in Stage IV Non-Small Cell Lung Cancer

(AstraZeneca) Nov 16, 2018 - AstraZeneca and MedImmune, its global biologics research and development arm, today announced final overall survival (OS) results for the Phase III MYSTIC trial, a randomised, open-label, multi-centre, global trial of Imfinzi (durvalumab) monotherapy and the combination of Imfinzi and tremelimumab, an anti-CTLA4 antibody, versus standard-of-care (SoC) platinum-based chemotherapy in previously-untreated patients with Stage IV (metastatic) non-small cell lung cancer (NSCLC). In the primary analysis population of patients, whose tumours express PD-L1 on 25% or more of their cancer cells as determined by the VENTANA PD-L1 (SP263) Assay, Imfinzi monotherapy and the combination of Imfinzi plus tremelimumab did not meet the primary endpoints of improving OS compared to SoC chemotherapy. While the OS result did not meet statistical significance, a hazard ratio (HR) of 0.76 (97.54% CI 0.564-1.019; nominal p=0.036) was observed with Imfinzi monotherapy. The combination therapy had an HR of 0.85 (98.77% CI 0.611-1.173; nominal p=0.202); the data support further analysis in exploratory subgroups.

Read Article arrow

H. Jack West, MD (Posted: November 16, 2018)

quotesI think there are a few key findings. First, obviously nothing here changes our standard of care in advanced NSCLC. Second, the durvalumab arm was statistically negative but had a hazard ratio for OS of 0.76, negative just due to prior alpha spending. These results don't supplant pembro in first line NSCLC, but don't represent a true failure of durvalumab that should lead us to question using it in a setting like stage III NSCLC, where consolidation durvalumab was highly positive for a PFS & OS benefit on the PACIFIC trial. Third, the durva/treme arm looked worse. This may be due to toxicity limiting ability to treat. Regardless, I think we should have very little enthusiasm for this combination. We will need to see whether nivolumab/ipilimumab suffers the same date and whether selection by tumor mutational burden in IO combinations pans out.quotes

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