Prior Treatment With PD-1/PD-L1 Inhibitors Improves Responses to Salvage Chemotherapy in NSCLC

Excerpt:

“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).”

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IMpower150 Trial Delays Progression in Advanced NSCLC With Atezolizumab/Bevacizumab Combo

Excerpt:

“In topline results announced from the phase III IMpower150 trial, atezolizumab (Tecentriq) in combination with bevacizumab (Avastin) and chemotherapy delayed progression or death when compared with bevacizumab and chemotherapy alone for patients with advanced nonsquamous non–small cell lung cancer (NSCLC).

“The co-primary endpoints for the IMpower150 study were progression-free survival (PFS) and overall survival (OS). Although exact numbers have not yet been released, Roche, the manufacturer of the anti–PD-L1 and anti–VEGF agents, called the reduction in progression or death with the addition of atezolizumab a ‘clinically meaningful reduction’ in a press release. At the interim analysis, data for OS were not yet mature, with the company labeling the findings as ‘encouraging.’ ”

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Update Sustains Osimertinib Activity Against CNS Mets in NSCLC

Excerpt:

“New results again demonstrated the benefit of frontline osimertinib (Tagrisso) in patients with EGFR-positive advanced non–small cell lung cancer (NSCLC) and CNS metastases at baseline, according to data presented at the 2017 ESMO Asia Congress.

“The subgroup analysis from the phase III FLAURA trial included 128 patients with at least 1 measurable and/or nonmeasurable CNS lesion at baseline. Among 61 patients who received osimertinib, the CNS objective response rate (ORR) was 66%, compared to 43% (odds ratio, 2.5; 95% CI 1.2-5.2; P = .011) in 67 patients who received standard EGFR TKI therapy with erlotinib (Tarceva) or gefitinib (Iressa).”

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Atezolizumab plus Bevacizumab and Chemotherapy Extends PFS in Non-Small Cell Lung Cancer

Excerpt:

“The addition of atezolizumab to first-line treatment with bevacizumab and chemotherapy significantly prolonged PFS among individuals with advanced nonsquamous non-small cell lung cancer, according to the agent’s manufacturer.

Atezolizumab (Tecentriq, Genentech) is a monoclonal antibody designed to bind with PD-L1.

“The randomized, multicenter, open-label phase 3 IMpower150 study assessed the efficacy and safety of atezolizumab in combination of chemotherapy with or without bevacizumab (Avastin, Genentech) for patients with stage IV nonsquamous NSCLC who had not undergone chemotherapy for their advanced disease.”

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Bevacizumab Does Not Improve Outcomes With Chemotherapy in Early NSCLC

Excerpt:

“The addition of bevacizumab to adjuvant chemotherapy failed to improve survival outcomes in patients with surgically resected early-stage non–small-cell lung cancer (NSCLC), according to a new randomized trial. The agent “does not have a role” in this setting, the investigators concluded.

” ‘In the setting of advanced-stage NSCLC, the first agent to improve survival when added to a platinum doublet was bevacizumab,’ wrote authors led by Heather A. Wakelee, MD, of the Stanford Cancer Institute at Stanford University in California. The researchers tested whether the VEGF-targeted agent would be similarly effective in the early-stage NSCLC adjuvant setting, where patients remain at high risk of relapse despite chemotherapy.”

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NKTR-214/Nivolumab Combination Shows Promise in Early Study

Excerpt:

“The combination of the CD122-biased cytokine NKTR-214 and the PD-1 inhibitor nivolumab (Opdivo) demonstrated target lesion reductions of 72% for patients with advanced cancers, according to findings from the phase Ib PIVOT-02 trial presented at the 2017 SITC Annual Meeting.

“The dose escalation trial enrolled patients in the first- or second-line setting with advanced non–small cell lung cancer (NSCLC), renal cell carcinoma (RCC), and melanoma. The objective response rates (ORR) by RECIST criteria ranged from 46% to 75% across tumor types. Additionally, the combination was tolerable, with no discontinuations attributed to adverse events (AEs).”

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FDA Approves Roche’s Alecensa (Alectinib) as First-Line Treatment for People With Specific Type of Lung Cancer

Excerpt:

“Roche (SIX: RO, ROG; OTCQX: RHHBY) today announced that the US Food and Drug Administration (FDA) approved the supplemental New Drug Application (sNDA) for Alecensa® (alectinib) for the treatment of people with anaplastic lymphoma kinase (ALK)-positive metastatic non-small cell lung cancer (NSCLC) as detected by an FDA-approved test. The approval is based on results from the phase III ALEX study, which showed Alecensa significantly reduced the risk of disease worsening or death (progression-free survival, PFS) by 47% (HR=0.53, 95% CI: 0.38, 0.73, p<0.0001) compared to crizotinib as assessed by independent review committee (IRC). Median PFS was 25.7 months (95% CI: 19.9, not estimable) for people who received Alecensa compared with 10.4 months (95% CI: 7.7, 14.6) for people who received crizotinib. The safety profile of Alecensa was consistent with that observed in previous studies. The study also showed that Alecensa significantly reduced the risk of the cancer spreading to or growing in the brain or central nervous system (CNS) compared to crizotinib by 84% (HR=0.16, 95% CI: 0.10, 0.28, p<0.0001). This was based on a time to CNS progression analysis in which there was a lower risk of progression in the CNS as the first site of disease progression for people who received Alecensa (12%) compared to people who received crizotinib (45%).”

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Osimertinib Continues to Show Impressive Activity in EGFR+ NSCLC

Excerpt:

“Osimertinib (Tagrisso) has impressed researchers in the field of EGFR-mutant non–small cell lung cancer (NSCLC), most recently with results from the phase III FLAURA trial solidifying its benefit.

“In FLAURA, treatment with frontline osimertinib led to a median progression-free survival (PFS) of 18.9 months (95% CI, 15.2-21.4). This represented a 54% risk reduction in progression or death compared with a standard EGFR tyrosine kinase inhibitor (TKI) for patients with locally advanced or metastatic EGFR-mutant NSCLC.”

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Immune-Related Adverse Events Predict Efficacy of Nivolumab in NSCLC

Excerpt:

“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.”

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