MD Conference Express - ELCC 2015 - (Page 28)

SELECTED UPDATES Immunotherapy Is Evolving and Promising for Lung Cancer Written by Kathy Boltz, PhD Promising immunotherapies are in development for lung cancer. Many combinations with these drugs are being investigated, though caution on provoking the immune system is needed. Anticancer vaccines have had limited success for lung cancer. Finally, clinical trials are evolving as therapies rapidly change. CHECKPOINT INHIBITORS Peer-Reviewed Highlights From the European Society for Medical Oncology 2015 European Lung Cancer Conference April 15-18, 2015 Geneva, Switzerland Lung tumors and melanomas display many more mutations than average and have about 200 nonsynonymous mutations per tumor, explained Solange Peters, MD, PhD, Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. In the clinic, immune checkpoint inhibitors target programmed cell death (PD-1), programmed death ligand (PD-L1), and cytotoxic T-lymphocyte-associated protein 4 (CTLA-4), which all help cancer to avoid immune destruction. Most PD-1 or PD-L1 inhibitors have reached late-phase development. Across studies, said Prof Peters, the response rate to anti-PD-1/PD-L1 inhibitors in unselected patients is 12% to 25%, though benefit is probably better translated by overall survival (OS) data. Checkpoint responses in non-small cell lung cancer (NSCLC) include unconventional, "immune-related" responses in not more than 5% of patients, with persistent reduction in target lesions or regression following initial progression, which results in the applicability of the usual RECIST criteria in this setting. The safety profile of checkpoint inhibitors is manageable, and > 3 years of follow-up data on nivolumab have found no new safety signals. A phase 3 trial of nivolumab in advanced, squamous cell NSCLC was recently stopped early due to superior OS with nivolumab treatment (median OS, 9.2 months; 95% CI, 7.3 to 13.3) vs docetaxel (median OS, 6.0 months; 95% CI, 5.1 to 7.3; P = .00025) [Opdivo (package insert). Princeton, NJ: Bristol-Myers Squibb Company; 2015]. A pooled analysis of pembrolizumab used as first- and subsequent-line monotherapy found that tumors shrank for 58% of patients, according to RECIST central review [Garon EB et al. ESMO 2014 (abstr LBA43)]. The response was lasting in patients for whom pembrolizumab had activity. Data are also emerging for the PD-L1 inhibitors MPLD3280A and MEDI4736. Predicting responsive subgroups is difficult. Smokers respond more than nonsmokers, but never-smokers also respond, including EGFR-mutated, partial-response, anaplastic lymphoma kinase-rearranged tumors. Level of PD-L1 expression has not had a clear association with response rate, progression-free survival (PFS), or OS. PD-L1 is not a reliable biomarker to date, and its evaluation still needs to be refined. Its expression is dynamic not only on tumor cells but also in immune cells, and it is evaluated differently in different trials. COMBINATION STRATEGIES While the old misperception was that chemotherapy did not interact with the immune system, the current goal is to increase survival through combinations and sequencing of immunotherapy, chemotherapy, and other therapies, said Martin Reck, MD, PhD, Lung Clinic Grosshansdorf, Grosshansdorf, Germany. However, safety is always a concern. Many chemotherapy and immunotherapy combinations are now in phase 3 trials. Combining PD-1 inhibition with an EGFR-tyrosine kinase inhibitor may be an option for patients without the T790M mutation in EGFR, but more data are needed. Radiation therapy may increase PD-L1 expression and prime response to immunotherapy. The abscopal effect was reported in a treatment-refractory lung cancer patient who received radiation therapy and ipilimumab, resulting in his tumor shrinking (Figure 1) [Golden EB et al. Cancer Immunol Res. 2013]. Combining immunotherapies must be done with caution, however, as multiple studies have reported high rates of adverse events and treatment discontinuation. 28 May 2015 www.mdce.sagepub.com http://mdc.sagepub.com/

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MD Conference Express - ELCC 2015