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ONCAlert | Upfront Therapy for mRCC

Case 1: Immunotherapy in Locally Advanced NSCLC

Targeted Oncology
Published Online:1:05 PM, Wed September 12, 2018


EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Benjamin P. Levy, MD:
Before we get into the discussion of how we would approach this patient, it may be important to frame the discussion and talk about the recent data we have, as it’s relevant to this case. The first piece of data that is relevant to this case is obviously the role of immunotherapy post-concurrent chemoradiation, which I think has altered our treatment paradigm in the past 6 to 12 months.

This paper was published in the New England Journal of Medicine in 2017. It’s the PACIFIC study. It looked at more than 700 patients who had stage III locally advanced unresectable non–small cell lung cancer with a performance status of 1 or less. If they had achieved at least stable disease after concurrent chemoradiation, they were randomized, 2:1, to consolidation durvalumab, a PD-L1 [programmed-cell death ligand 1] drug, every 2 weeks, versus placebo.

The tumor and patient characteristics were well balanced between the 2 arms. Importantly, all PD-L1 patients were allowed. Patients were not allowed to get consolidation chemotherapy. They could get induction chemotherapy. The PFS [progression-free survival] Kaplan–Meier curves are shown here, and there was a robust benefit with the addition of consolidation durvalumab versus placebo. As it relates to PFS, the hazard ratio was 0.52. There was a median PFS of 16.8 months versus 5.6 months. It seemed like all subgroups benefitted in the experimental arm—patients who were smokers or non-smokers, with stage IIIA or IIIB disease, and with squamous or nonsquamous histology. These patients did seem to have a benefit in progression-free survival. There was also an improvement in response rate with durvalumab versus placebo.

Not surprisingly, there were adverse events encountered from the study, but I don’t think any of us thought that this drug would be as well-tolerated as it was, being that it was given so close to radiation. We didn’t see a lot of pneumonitis from this trial. Grade 3/4 adverse events were not that frequent in the immunotherapy arm as compared to the placebo arm. So, I think that’s one piece that’s practice-changing, that we can talk about with this case—the role of durvalumab in benefitting all patients. We know that there’s an overall survival advantage. We don’t know what that is yet, as of today, but there is certainly a meaningful benefit in PFS.

The second data point that I just want to talk about before we go back to the case has recently been published in the Journal of Clinical Oncology. It looked at the role of checkpoint inhibitors in patients who have preexisting autoimmune disorders. This was a retrospective analysis from multiple institutions, including MD Anderson Cancer Center and Memorial Sloan Kettering Cancer Center, that looked at 56 patients who had preexisting autoimmune disorders and were treated with a checkpoint inhibitor. These autoimmune disorders could be anything from rheumatoid arthritis, to ulcerative colitis, to multiple sclerosis. There were a couple of patients there. Most of these patients were not symptomatic. These weren’t patients with any sort of symptoms at the time that they were looked at in this retrospective analysis. Most of these patients also didn’t require any medications for their autoimmune disease. Of the patients who received a checkpoint inhibitor, only 23% developed a flare of their autoimmune disorder. I thought that was interesting. We can talk about how comfortable we feel in this case, when treating with immunotherapy.

When we look at the cumulative incidence or the exacerbation of the autoimmune disorder versus the cumulative incidence of death and disease progression, we see that most of these patients were allowed to continue on their treatment. Very few of these patients had any long-term treatment interruptions with immunotherapy. So, the take-home message from this retrospective analysis was that it may be safe to give checkpoint inhibitors in patients with preexisting autoimmune disorders.

Transcript edited for clarity.


EXPERT PERSPECTIVE VIRTUAL TUMOR BOARD

Benjamin P. Levy, MD:
Before we get into the discussion of how we would approach this patient, it may be important to frame the discussion and talk about the recent data we have, as it’s relevant to this case. The first piece of data that is relevant to this case is obviously the role of immunotherapy post-concurrent chemoradiation, which I think has altered our treatment paradigm in the past 6 to 12 months.

This paper was published in the New England Journal of Medicine in 2017. It’s the PACIFIC study. It looked at more than 700 patients who had stage III locally advanced unresectable non–small cell lung cancer with a performance status of 1 or less. If they had achieved at least stable disease after concurrent chemoradiation, they were randomized, 2:1, to consolidation durvalumab, a PD-L1 [programmed-cell death ligand 1] drug, every 2 weeks, versus placebo.

The tumor and patient characteristics were well balanced between the 2 arms. Importantly, all PD-L1 patients were allowed. Patients were not allowed to get consolidation chemotherapy. They could get induction chemotherapy. The PFS [progression-free survival] Kaplan–Meier curves are shown here, and there was a robust benefit with the addition of consolidation durvalumab versus placebo. As it relates to PFS, the hazard ratio was 0.52. There was a median PFS of 16.8 months versus 5.6 months. It seemed like all subgroups benefitted in the experimental arm—patients who were smokers or non-smokers, with stage IIIA or IIIB disease, and with squamous or nonsquamous histology. These patients did seem to have a benefit in progression-free survival. There was also an improvement in response rate with durvalumab versus placebo.

Not surprisingly, there were adverse events encountered from the study, but I don’t think any of us thought that this drug would be as well-tolerated as it was, being that it was given so close to radiation. We didn’t see a lot of pneumonitis from this trial. Grade 3/4 adverse events were not that frequent in the immunotherapy arm as compared to the placebo arm. So, I think that’s one piece that’s practice-changing, that we can talk about with this case—the role of durvalumab in benefitting all patients. We know that there’s an overall survival advantage. We don’t know what that is yet, as of today, but there is certainly a meaningful benefit in PFS.

The second data point that I just want to talk about before we go back to the case has recently been published in the Journal of Clinical Oncology. It looked at the role of checkpoint inhibitors in patients who have preexisting autoimmune disorders. This was a retrospective analysis from multiple institutions, including MD Anderson Cancer Center and Memorial Sloan Kettering Cancer Center, that looked at 56 patients who had preexisting autoimmune disorders and were treated with a checkpoint inhibitor. These autoimmune disorders could be anything from rheumatoid arthritis, to ulcerative colitis, to multiple sclerosis. There were a couple of patients there. Most of these patients were not symptomatic. These weren’t patients with any sort of symptoms at the time that they were looked at in this retrospective analysis. Most of these patients also didn’t require any medications for their autoimmune disease. Of the patients who received a checkpoint inhibitor, only 23% developed a flare of their autoimmune disorder. I thought that was interesting. We can talk about how comfortable we feel in this case, when treating with immunotherapy.

When we look at the cumulative incidence or the exacerbation of the autoimmune disorder versus the cumulative incidence of death and disease progression, we see that most of these patients were allowed to continue on their treatment. Very few of these patients had any long-term treatment interruptions with immunotherapy. So, the take-home message from this retrospective analysis was that it may be safe to give checkpoint inhibitors in patients with preexisting autoimmune disorders.

Transcript edited for clarity.
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