MedicalResearch.com Interview with:
Florence K Keane MD
Resident, Radiation Oncology
Harvard Radiation Oncology Program
MedicalResearch.com: What is the background for this study?
Response: Checkpoint inhibitors (CPIs) have recently transformed the management of patients with metastatic lung cancer, demonstrating significant improvements in overall and progression-free survival in both the first-line setting in patients with increased expression of PD-L1 (≥50%) and in patients with previously treated NSCLC who have progressed on chemotherapy. CPIs are also moving into the treatment of patients with localized lung cancer, with the recently published PACIFIC trial demonstrating a significant improvement in progression-free survival in patients with inoperable stage III NSCLC treated with adjuvant durvalumab after definitive chemoradiotherapy.
However, CPIs are associated with unique toxicities as compared to cytotoxic chemotherapy, including pulmonary, endocrine, neurologic, gastrointestinal, and dermatologic adverse events, which may be fatal in some cases. The risk of autoimmune pneumonitis with checkpoint inhibitors is estimated to be on the order of 5%. Many patients with lung cancer will require radiotherapy for palliation of symptoms. Thoracic radiotherapy (TRT) is also a risk factor for pneumonitis, with a dose- and volume-dependent impact on risk. However, it is unknown whether treatment with CPIs and TRT is associated with increased risk of toxicity.
MedicalResearch.com: What are the main findings?
Response: In this retrospective analysis of 164 patients with metastatic lung cancer treated with checkpoint inhibitors between 2013 and 2016, we compared rates of toxicity and overall survival in patients receiving thoracic radiotherapy in addition to CPIs.
We found that thoracic radiotherapy in addition to checkpoint inhibitors was not associated an increased risk of grade ≥2 immune-related adverse events (IRAEs) including pneumonitis as compared to CPIs alone. Of note, the majority of patients received RT prior to CPIs. Reassuringly, in the 16 patients treated with TRT after or between cycles of CPI, there was also no increased risk of toxicity, including pneumonitis. On multivariate analysis, there was an improvement in overall survival in patients treated with fewer lines of chemotherapy and patients with grade ≥2 adverse events.
MedicalResearch.com: What should readers take away from your report?
Response: Our findings suggest that treatment with TRT and checkpoint inhibitors is not associated with a significantly increased risk of IRAEs, including pneumonitis. These data are reassuring, especially as many patients with metastatic lung cancer will require radiotherapy during their disease course, and the long half-life of CPIs often precludes a wash-out period.
The trend towards improved survival with the use of TRT is particularly intriguing. The potential for radiotherapy to stimulate and/ or potentiate the efficacy of immunotherapy is an area of ongoing research.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: As noted above, most patients in our cohort received radiotherapy several months prior to CPIs. Larger cohorts and prospective study of concurrent RT and CPIs are needed to further evaluate the potential toxicity of concurrent treatment, and to determine the optimal role of radiotherapy in the era of immunotherapy.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Hwang WL, Niemierko A, Hwang KL, Hubbeling H, Schapira E, Gainor JF, Keane FK. Clinical Outcomes in Patients With Metastatic Lung Cancer Treated With PD-1/PD-L1 Inhibitors and Thoracic Radiotherapy. JAMA Oncol. Published online September 27, 2017. doi:10.1001/jamaoncol.2017.3808
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