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How Durvalumab Has Changed the Standard of Care

Insights From: Nicolas Girard, MD, Curie Institute
Published: Thursday, May 09, 2019



Transcript:

Nicolas Girard, MD:
So the PACIFIC trial is a randomized phase III trial that compared durvalumab with placebo. This is a double-blind design, and this study focused on patients who completed chemoradiotherapy. It was concurrent chemoradiation, meaning that the patient had at least 2 cycles of chemotherapy during the delivery of radiation. This is a very large trial, more than 700 patients. So randomization was done within 6 weeks after completion of radiation, and the duration of durvalumab or placebo treatment was 1 year, and durvalumab was delivered at 10 mg/kg every 2 weeks.

The results of PACIFIC show, in terms of PFS [progression free survival], a very significant benefit with a hazard ratio of 0.51, meaning that the median PFS with durvalumab was more than 17 months versus 5 months with the placebo. So this is clearly a paradigm change for the management of those patients. Historically, chemoradiation was very disappointing because it’s a treatment that requires chemotherapies and delivery of radiation every day for 6 weeks. You may experience some toxicities. And at the end, 5 months after completion of this aggressive treatment, relapse occurs in more than half of the patients. So clearly, we show with the durvalumab treatment, this consolidation treatment, that we can improve the outcome of the patient. And this PFS benefit translates into an overall survival benefit with 2 years’ survival moving from 56% to 66%, which was highly significant.

Durvalumab is now available in France. Actually, we had a program, meaning an expanded-access program, that started just after the presentation and the publication of the PFS benefit with durvalumab. So we started durvalumab treatment for patients something like 18 months ago. Clearly, durvalumab consolidation is now a standard of care, so we have the approval in Europe and in France. In France we still need to have the negotiation. But the product, durvalumab, is actually available in the clinic for the patient but on approval. And the level of the approval is consolidation after chemoradiotherapy in PD-L1 [programmed death-ligand 1]–positive non–small cell lung cancer.

In my practice, all eligible patients actually receive durvalumab consolidation. I mean patients who had a concurrent chemoradiotherapy without any remaining toxicity after completion of this program. And at the end, it represents about 70% of those patients, but on PD-L1 positivity. So clearly, we have an option that is delivered to a majority of patients with stage III unresectable non–small cell lung cancer.

In my practice, based on this close collaboration that we have with radiation oncologists, we are planning everything for the patient at the time of initiation of chemotherapy and radiotherapy. In my center, it’s not very easy to start everything, chemotherapy and radiotherapy, the same day. So usually patients do receive 1 of 2 cycles of chemotherapy as induction treatment followed by the concurrent chemoradiation phase. So the patients have close clinical follow-up by the radiation oncologist.

And at this time, the patient got something like 50 grays, meaning that the remaining duration of radiotherapy will be 1 or 2 weeks. We plan everything, meaning the CT [computed tomography] scan assessment 2 weeks after completion of the last dose of radiation and the consultation with myself or another member of the team. And this way we have an early assessment of the disease status, so we need to make sure that there is no disease progression. So we are taking data from brain imaging by MRI [magnetic resonance imaging] or CT scan. It means that 2 weeks after completion of radiation, we have a clear assessment of the disease and we can plan the initiation of durvalumab, usually within the week following this consolidation. So a majority of patients actually initiate durvalumab within 3 weeks after completion of radiation. One key point in this early assessment is also to make sure that we have a complete recovery of potential toxicities of the chemoradiation program, which is actually the case for majority of the patients.

Transcript Edited for Clarity
 
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Transcript:

Nicolas Girard, MD:
So the PACIFIC trial is a randomized phase III trial that compared durvalumab with placebo. This is a double-blind design, and this study focused on patients who completed chemoradiotherapy. It was concurrent chemoradiation, meaning that the patient had at least 2 cycles of chemotherapy during the delivery of radiation. This is a very large trial, more than 700 patients. So randomization was done within 6 weeks after completion of radiation, and the duration of durvalumab or placebo treatment was 1 year, and durvalumab was delivered at 10 mg/kg every 2 weeks.

The results of PACIFIC show, in terms of PFS [progression free survival], a very significant benefit with a hazard ratio of 0.51, meaning that the median PFS with durvalumab was more than 17 months versus 5 months with the placebo. So this is clearly a paradigm change for the management of those patients. Historically, chemoradiation was very disappointing because it’s a treatment that requires chemotherapies and delivery of radiation every day for 6 weeks. You may experience some toxicities. And at the end, 5 months after completion of this aggressive treatment, relapse occurs in more than half of the patients. So clearly, we show with the durvalumab treatment, this consolidation treatment, that we can improve the outcome of the patient. And this PFS benefit translates into an overall survival benefit with 2 years’ survival moving from 56% to 66%, which was highly significant.

Durvalumab is now available in France. Actually, we had a program, meaning an expanded-access program, that started just after the presentation and the publication of the PFS benefit with durvalumab. So we started durvalumab treatment for patients something like 18 months ago. Clearly, durvalumab consolidation is now a standard of care, so we have the approval in Europe and in France. In France we still need to have the negotiation. But the product, durvalumab, is actually available in the clinic for the patient but on approval. And the level of the approval is consolidation after chemoradiotherapy in PD-L1 [programmed death-ligand 1]–positive non–small cell lung cancer.

In my practice, all eligible patients actually receive durvalumab consolidation. I mean patients who had a concurrent chemoradiotherapy without any remaining toxicity after completion of this program. And at the end, it represents about 70% of those patients, but on PD-L1 positivity. So clearly, we have an option that is delivered to a majority of patients with stage III unresectable non–small cell lung cancer.

In my practice, based on this close collaboration that we have with radiation oncologists, we are planning everything for the patient at the time of initiation of chemotherapy and radiotherapy. In my center, it’s not very easy to start everything, chemotherapy and radiotherapy, the same day. So usually patients do receive 1 of 2 cycles of chemotherapy as induction treatment followed by the concurrent chemoradiation phase. So the patients have close clinical follow-up by the radiation oncologist.

And at this time, the patient got something like 50 grays, meaning that the remaining duration of radiotherapy will be 1 or 2 weeks. We plan everything, meaning the CT [computed tomography] scan assessment 2 weeks after completion of the last dose of radiation and the consultation with myself or another member of the team. And this way we have an early assessment of the disease status, so we need to make sure that there is no disease progression. So we are taking data from brain imaging by MRI [magnetic resonance imaging] or CT scan. It means that 2 weeks after completion of radiation, we have a clear assessment of the disease and we can plan the initiation of durvalumab, usually within the week following this consolidation. So a majority of patients actually initiate durvalumab within 3 weeks after completion of radiation. One key point in this early assessment is also to make sure that we have a complete recovery of potential toxicities of the chemoradiation program, which is actually the case for majority of the patients.

Transcript Edited for Clarity
 
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