VJVirtual | Managing oligoprogressive NSCLC during immune checkpoint inhibitor therapy

Over the course of recent years, there is an emerging trend of non-small cell lung carcinoma patients treated with immune checkpoint inhibitors developing oligoprogressive disease, or OPD, which is typically defined as five or fewer lesions and managed with local treatments. But this can be challenging when making clinical decisions to decide which patients would be ideal candidates for local treatment, such as radiation, versus those who should switch to another systemic agent. There’s also positive data regarding outcomes following radiation to optimize treatment management strategy for these patients. So we essentially performed a multinational study as a collaboration between Oxford University Hospitals, Guy’s and St. Thomas Hospital in London, and the Dana-Farber Cancer Institute in Boston, for which the preliminary findings were also presented as an oral presentation at the annual meeting. Our team primarily aimed to identify clinical and pathological factors in non-small cell lung carcinoma that can improve stratification of patients most likely to benefit from radiation for oligoprogressive disease with or without ICA continuation versus those who should switch to alternative systemic agents. So we essentially looked at over 1,100 patients and identified 103 eligible candidates. There were three main outcomes consisting of local control, progression-free survival, and overall survival. The median age of patients who were diagnosed with OPD was 68 years, with a higher preponderance towards female patients. Patients had been receiving immunotherapy for a median duration of five and a half months, after which most patients developed a single OPD lesion, primarily in the lung, which was managed with both stereotactic and non-stereotactic radiation. In the complete cohort, the median local control of radiated lesions was not reached. The median PFS was 6.9 months, and the median OS was 23.46 months. We explored multiple patient-specific factors, such as the age at OPD diagnosis, gender, smoking status, PD-L1 score, KPS status, number of OPD lesions, cumulative OPD lesion volume, and none of these factors were associated with the three evaluated outcomes. But we did observe that patients harboring visceral OPD lesions were in fact associated with an improvement in PFS. We next looked at the impact of treatment-specific factors and outcomes, such as radiation modality and response of OPD lesions to immunotherapy, which were not associated with all three outcomes. But we did notice that patients receiving intermediate to high-dose radiation or those achieving local response to radiation were in fact associated with an improvement in local control and overall survival. We also observed that patients who had received more than five and a half months of immunotherapy before OPD diagnosis were also associated with an improvement in overall survival. In terms of toxicity, overall the treatment was well-tolerated with no severe adverse events associated with radiation, but we did notice that there were five cases of severe pneumonitis which were attributed to immunotherapy. I think it’s also interesting to note that after completing radiation, 65% of the patients resumed systemic treatment with the same immunotherapy regimen, and we also observed that there were nine patients who had completed radiation and were off systemic therapy. They had in fact achieved prolonged PFS, which ranged from 13.8 to 50 months. And this again highlights the fact that radiation can be effective in extending immune-mediated tumor control in a subset of non-small cell lung carcinoma patients treated with immunotherapy. In summary, we have found multiple factors of clinical interest, which can be useful in guiding multidisciplinary clinical decisions to optimize management of well-selected patients with oligoprogression and having non-small cell lung carcinoma. And these findings need to be validated in larger prospectively designed clinical studies.

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