“Immune checkpoint inhibitors have significantly reshaped the treatment landscape of advanced non-small cell lung cancer (NSCLC) in the second-line and, more recently, in the first-line setting. However, only a subset of patients achieves a durable response on immunotherapy, and it is not clear whether prior immunotherapy treatment impacts response to salvage chemotherapy.
“A recent retrospective study evaluated responses to salvage chemotherapy in 73 patients with advanced NSCLC who had progressed on prior PD-1/PD-L1 inhibitors. Ten of the 73 patients had received immunotherapy as first-line treatment, while the remaining 63 patients had received immunotherapy as second-line treatment following first-line chemotherapy. Response to salvage chemotherapy was compared to response to the last chemotherapy administered before immunotherapy (LCBI).”
“Neoadjuvant treatment with the combination of nivolumab (Opdivo) and ipilimumab (Yervoy) demonstrated almost a tripling in objective response rate (ORR) compared with the PD-1 inhibitor alone but at the cost of significant added grade 3 adverse events (AEs) for patients with high-risk resectable melanoma, according to a small study presented at the 2017 SITC Annual Meeting.
“In the combination arm (n = 11), the ORR was 73% and 50% of patients achieved a pathological complete response (pCR). With nivolumab alone (n = 12), the ORR was 25% and the pCR rate was 25%. Unfortunately, these gains in response were accompanied by 73% of patients in the combination arm having a grade 3 AE compared with just 8% in the single-agent arm. This high level of toxicity led the researchers to close the study early, according to Sangeetha M. Reddy, MD, MSci. Reddy worked on this trial with co-investigators Rodabe Amaria, MD, and Jennifer Wargo, MD.”
“Inovio Pharmaceuticals, Inc. (NASDAQ:INO) today initiated a phase 1b/2a immuno-oncology trial in patients with newly diagnosed glioblastoma (GBM) designed to evaluate cemiplimab (also known as REGN2810), a PD-1 inhibitor developed by Regeneron Pharmaceuticals, Inc.(NASDAQ:REGN), in combination with Inovio’s INO-5401 T cell activating immunotherapy encoding multiple antigens and INO-9012, an immune activator encoding IL-12.”
“While immunotherapy with programmed death receptor 1 (PD-1) inhibiting antibodies has revolutionized the treatment of non-small cell lung cancer (NSCLC), use of these agents comes at the cost of potential serious immune-related adverse events (irAEs). In melanoma, development of cutaneous irAEs, such as rash and vitiligo, during treatment with PD-1 inhibitors has been shown to be associated with survival benefit, suggesting that early onset of irAEs may predict treatment outcomes. However, in NSCLC, the predictive value of immunotherapy-related toxicity as a clinical marker for efficacy to PD-1 inhibition is unknown. A multi-institution retrospective study investigated the relation between the development of irAEs and efficacy of PD-1 inhibitors in 134 patients with advanced or recurrent NSCLC who received second-line treatment with nivolumab. The primary outcome for this analysis was progression-free survival (PFS) according to the development of irAEs in a 6-week landmark analysis.”
“The FDA granted priority review to nivolumab for the treatment of patients with melanoma who are at high risk for disease recurrence following complete surgical resection, according to the drug’s manufacturer.
“Nivolumab (Opdivo, Bristol-Myers Squibb), a PD-1 checkpoint inhibitor, previously received breakthrough therapy designation for this indication.”
“Patients with melanoma continued to experience tumor response to nivolumab monotherapy when treated beyond progression, according to a pooled analysis of data from the CheckMate 066 and CheckMate 067 studies.
” ‘The results of this analysis suggest that continued treatment with nivolumab [Opdivo, Bristol-Myers Squibb] may be an option to achieve further apparent clinical benefit in some patients with advanced melanoma,’ Georgina V. Long, PhD, BSc, MBBS, FRACP, chair of melanoma medical oncology and translational research at Melanoma Institute Australia and Royal North Shore Hospital of The University of Sydney in Sydney, Australia, and colleagues wrote.”
“Patients with glioblastoma multiforme, a type of brain cancer, who recurred following radiation therapy and Temodal (temozolomide), did not survive longer when treated with the PD-1 inhibitor Opdivo (nivolumab) compared to standard-of-care treatment with Avastin (bevacizumab).
The findings mean that the randomized CheckMate -143 Phase 3 trial (NCT02017717) has failed to meet its primary objective.
” ‘[Glioblastoma multiforme] is a historically difficult disease to treat and conventional treatment options have demonstrated limited responses,’ Fouad Namouni, MD, head of Oncology Development and head of Medical at Bristol-Myers Squibb, said in a news release. ‘We remain steadfast in our pursuit of treatments for diseases with the highest unmet need and continue our work to determine how our immuno-oncology agents can potentially improve outcomes for these patients.’ ”
“Immunotherapy agents, both as monotherapy and in combination, are emerging in the pipeline of non–small cell lung cancer (NSCLC) and could end up competing as frontline treatment for patients, explains Sukhmani Padda, MD.
“For example, the PD-1 inhibitor pembrolizumab (Keytruda) is the sole immunotherapy agent approved in the first-line setting for patients with NSCLC; however, many other immunotherapy agents and combination regimens are in development that are aimed at this line of therapy.”
“Statistical modeling of long-term survival from the KEYNOTE trials of the programmed cell death protein 1 (PD-1)–inhibitor pembrolizumab (Keytruda) estimates that one-quarter of appropriately selected patients with advanced non–small cell lung cancer (NSCLC) may attain long-term survival.
” ‘In the context of the pembrolizumab program, these are the furthest-out data that we have so far, and I think they represent a remarkable step forward,’ commented Matthew D. Hellmann, MD, of Memorial Sloan Kettering Cancer Center, New York, who presented the analysis at the 2017 ASCO-SITC (Society for Immunotherapy of Cancer) Clinical Immuno-Oncology Symposium.”