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Immunotherapy in inoperable stage III non-small cell lung cancer: a review.

ABSTRACT: The leading cause of cancer-related deaths in the United States continues to be lung cancer. Approximately 25-30% of patients are diagnosed with locally advanced non-small cell lung cancer (NSCLC). Concurrent chemoradiation with a platinum-based doublet is the current standard of care for patients with inoperable stage III NSCLC. Unfortunately, only 15-20% of patients treated with definitive chemoradiation are alive at 5 years. Thus, there has been a major unmet need in this area. In this article, we summarize the current status and ongoing clinical trials incorporating immunotherapy into the management of inoperable stage III NSCLC, and we also present our perspective on the future directions.

SUBMITTER: Jain NA

PROVIDER: S-EPMC6586171 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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Immunotherapy in inoperable stage III non-small cell lung cancer: a review.

Jain Natasha A NA Otterson Gregory A GA

Drugs in context 20190617

The leading cause of cancer-related deaths in the United States continues to be lung cancer. Approximately 25-30% of patients are diagnosed with locally advanced non-small cell lung cancer (NSCLC). Concurrent chemoradiation with a platinum-based doublet is the current standard of care for patients with inoperable stage III NSCLC. Unfortunately, only 15-20% of patients treated with definitive chemoradiation are alive at 5 years. Thus, there has been a major unmet need in this area. In this articl ...[more]

PMID: 31258616

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Project description:BACKGROUND:Loco-regional and distant failure are common in inoperable stage III non small-cell lung cancer (NSCLC) after chemoradiotherapy (CRT). However, there is limited real-world data on failure pattern, patient prognosis and salvage options. METHODS:We analysed 99 consecutive patients with inoperable stage III NSCLC treated with CRT between 2011 and 2016. Follow up CT scans from date of the first-site failure were matched with the delivered radiation treatment plans. Intra-thoracic loco-regional relapse was defined as in-field (IFR) vs. out-of-field recurrence (OFR) [in- vs. outside 50Gy isodose line in the involved lung], respectively. Extracranial distant (DMs) and brain metastases (BMs) as first site of recurrence were also evaluated. Using the Kaplan-Meier method, impact of salvage surgery (sS), radiotherapy (sRT), chemotherapy (sCT) and immunotherapy (sIO) on patient survival was assessed. RESULTS:Median follow-up was 60.0?months. Median PFS from the end of CRT for the entire cohort was 7.5 (95% CI: 6.0-9.0?months) months. Twenty-six (26%) and 25 (25%) patients developed IFR and OFR. Median time to diagnosis of IFR and OFR was 7.2 and 6.2?months. In the entire cohort, onset of IFR and OFR did not influence patient outcome. However, in 73 (74%) patients who survived longer than 12?months after initial diagnosis, IFR was a significant negative prognostic factor with a median survival of 19.3 vs 40.0?months (p <?0.001). No patients with IFR underwent sS and/or sRT. 18 (70%) and 5 (19%) patients with IFR underwent sCT and sIO. Three (12%) patients with OFR underwent sS and are still alive with 3-year survival rate of 100%. 5 (20%) patients with OFR underwent sRT with a median survival of 71.2 vs 19.1?months (p =?0.014). Four (16%) patients with OFR received sIO with a numerical survival benefit (64.6 vs. 26.4?months, p =?0.222). DMs and BMs were detected in 27 (27%) and 16 (16%) patients after median time of 5.8 and 5.13?months. Both had no impact on patient outcome in the entire cohort. However, patients with more than three BMs showed significantly poor OS (9.3 vs 26.0?months; p =?0.012). CONCLUSIONS:After completion of CRT, IFR was a negative prognostic factor in those patients, who survived longer than 12?months after initial diagnosis. Patients with OFR benefit significantly from salvage local treatment. Patients with more than three BMs as first site of failure had a significantly inferior outcome.

Project description:Simple Summary The treatment of resectable stage III non-small-cell lung cancer with N2 lymph node involvement is usually multimodal and is generally based on neoadjuvant chemotherapy +/− radiotherapy followed by surgery, but the cure rate is still low. Immunotherapy based on anti-PD1/PD-L1 immune checkpoint inhibitors has improved survival in advanced and stage III non-resectable NSCLC patients and is being studied in earlier stages to improve the cure rate of lung cancer. In this article, we review all therapeutic approaches to stage III-N2 NSCLC, analysing both completed and ongoing studies that evaluate the addition of immunotherapy with or without chemotherapy and/or radiotherapy. Abstract Stage III non-small-cell lung cancer (NSCLC) with N2 lymph node involvement is a heterogeneous group with different potential therapeutic approaches. Patients with potentially resectable III-N2 NSCLC are those who are considered to be able to receive a multimodality treatment that includes tumour resection after neoadjuvant therapy. Current treatment for these patients is based on neoadjuvant chemotherapy +/− radiotherapy followed by surgery and subsequent assessment for adjuvant chemotherapy and/or radiotherapy. In addition, some selected III-N2 patients could receive upfront surgery or pathologic N2 incidental involvement can be found a posteriori during analysis of the surgical specimen. The standard treatment for these patients is adjuvant chemotherapy and evaluation for complementary radiotherapy. Despite being a locally advanced stage, the cure rate for these patients continues to be low, with a broad improvement margin. The most immediate hope for improving survival data and curing these patients relies on integrating immunotherapy into perioperative treatment. Immunotherapy based on anti-PD1/PD-L1 immune checkpoint inhibitors is already a standard treatment in stage III unresectable and advanced NSCLC. Data from the first phase II studies in monotherapy neoadjuvant therapy and, in particular, in combination with chemotherapy, are highly promising, with impressive improved and complete pathological response rates. Despite the lack of confirmatory data from phase III trials and long-term survival data, and in spite of various unresolved questions, immunotherapy will soon be incorporated into the armamentarium for treating stage III-N2 NSCLC. In this article, we review all therapeutic approaches to stage III-N2 NSCLC, analysing both completed and ongoing studies that evaluate the addition of immunotherapy with or without chemotherapy and/or radiotherapy.

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Immunotherapy in inoperable stage III non-small cell lung cancer: a review.

Publications

Immunotherapy in inoperable stage III non-small cell lung cancer: a review.

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