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Immunotherapy in Stage III NSCLC

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



Transcript:

Nicolas Girard, MD:
Now we have the data from the PACIFIC trial. The paradigm of treatment for a patient with unresectable stage III non–small cell lung cancer has changed because before chemoradiation was the sole treatment, and after the completion of radiation, the patient just had a follow-up. We had time to organize everything after completion of radiation. But now we clearly need to continue the treatment. First we need to plan everything before starting the treatment. At the time of diagnosis and after the discussion at the multidisciplinary tumor board, we know that the strategy will be chemoradiation followed by immunotherapy. We need to plan this together with the radiation oncology team because we know that at some point at the time of the last delivery of radiation, we will need to have a clear plan for the patient to get a CT [computed tomography] scan assessment and then an appointment with the medical oncologist to initiate consolidation with durvalumab.

And the second point is also toward the patient on both, meaning that the patient should be aware that the treatment sequence will be chemoradiation and then 1 year of immunotherapy. This is very important because chemoradiation is a treatment that is somehow aggressive from a patient standpoint. We have chemotherapy and radiation therapy every day. So at some point, there may be some toxicities that happen during this treatment delivery. At the end, the patient should be aware that the last radiation dose is not the end of the treatment sequence, but that immunotherapy is already planned, and that the treatment duration will be 1 year. This is very important to have the patient aware and fully informed about the treatment sequence.

In the setting of the approval of durvalumab in Europe, we need to test the tumor for PD-L1 [programmed death-ligand 1] expression because in Europe, the approval is restricted to PD-L1–positive tumors. So this is a paradigm change because it is a first biomarker to be mandatory in the setting of nonmetastatic non–small cell lung cancer. So we have to inform the pathologist, have them on board and assessing PD-L1 status. And this has to be done on the initial biopsy because otherwise, it will not be possible to assess PD-L1 status. It’s very difficult to do a rebiopsy after chemoradiation, for example, because usually you have inflammation in the lung, so it’s very difficult for me to do a rebiopsy after completion of chemoradiation.

On the other hand, from more global perspective, chemoradiation is a curative intent treatment. We do not expect to have any remaining tumor cell on biopsies performed after chemoradiation. If there are some active tumor cells on a rebiopsy performed after chemoradiation, what does that mean? Does that mean that the patient requires actually second-line treatment and not consolidation? Well, for me, this is why it’s so important to make sure to have the PD-L1 status before starting the chemoradiation treatment.

After a treatment sequence with chemoradiation followed by immunotherapy, obviously some patients will present with tumor recurrence. In my experience—very limited experience because we started to develop durvalumab now 1 year ago in France—I have some patients treated with durvalumab and who are still on treatment and who did not progress with this treatment. Still, I have some patients who had disease progression. A lot of patients progressed with only oligometastasis disease, especially brain metastasis, 1 single lesion. And in this situation, we have to be very pragmatic and actually treat the patient focally with, for example, stereotactic radiation therapy on the progressive lesion. And then we can discuss whether we need to continue durvalumab treatment. I have some patients who have systemic progression, but in my experience, this is not a majority of those patients.

Transcript Edited for Clarity
 
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Transcript:

Nicolas Girard, MD:
Now we have the data from the PACIFIC trial. The paradigm of treatment for a patient with unresectable stage III non–small cell lung cancer has changed because before chemoradiation was the sole treatment, and after the completion of radiation, the patient just had a follow-up. We had time to organize everything after completion of radiation. But now we clearly need to continue the treatment. First we need to plan everything before starting the treatment. At the time of diagnosis and after the discussion at the multidisciplinary tumor board, we know that the strategy will be chemoradiation followed by immunotherapy. We need to plan this together with the radiation oncology team because we know that at some point at the time of the last delivery of radiation, we will need to have a clear plan for the patient to get a CT [computed tomography] scan assessment and then an appointment with the medical oncologist to initiate consolidation with durvalumab.

And the second point is also toward the patient on both, meaning that the patient should be aware that the treatment sequence will be chemoradiation and then 1 year of immunotherapy. This is very important because chemoradiation is a treatment that is somehow aggressive from a patient standpoint. We have chemotherapy and radiation therapy every day. So at some point, there may be some toxicities that happen during this treatment delivery. At the end, the patient should be aware that the last radiation dose is not the end of the treatment sequence, but that immunotherapy is already planned, and that the treatment duration will be 1 year. This is very important to have the patient aware and fully informed about the treatment sequence.

In the setting of the approval of durvalumab in Europe, we need to test the tumor for PD-L1 [programmed death-ligand 1] expression because in Europe, the approval is restricted to PD-L1–positive tumors. So this is a paradigm change because it is a first biomarker to be mandatory in the setting of nonmetastatic non–small cell lung cancer. So we have to inform the pathologist, have them on board and assessing PD-L1 status. And this has to be done on the initial biopsy because otherwise, it will not be possible to assess PD-L1 status. It’s very difficult to do a rebiopsy after chemoradiation, for example, because usually you have inflammation in the lung, so it’s very difficult for me to do a rebiopsy after completion of chemoradiation.

On the other hand, from more global perspective, chemoradiation is a curative intent treatment. We do not expect to have any remaining tumor cell on biopsies performed after chemoradiation. If there are some active tumor cells on a rebiopsy performed after chemoradiation, what does that mean? Does that mean that the patient requires actually second-line treatment and not consolidation? Well, for me, this is why it’s so important to make sure to have the PD-L1 status before starting the chemoradiation treatment.

After a treatment sequence with chemoradiation followed by immunotherapy, obviously some patients will present with tumor recurrence. In my experience—very limited experience because we started to develop durvalumab now 1 year ago in France—I have some patients treated with durvalumab and who are still on treatment and who did not progress with this treatment. Still, I have some patients who had disease progression. A lot of patients progressed with only oligometastasis disease, especially brain metastasis, 1 single lesion. And in this situation, we have to be very pragmatic and actually treat the patient focally with, for example, stereotactic radiation therapy on the progressive lesion. And then we can discuss whether we need to continue durvalumab treatment. I have some patients who have systemic progression, but in my experience, this is not a majority of those patients.

Transcript Edited for Clarity
 
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