10 Key Lung Cancer Abstracts to be presented at ASCO 2016

H. Jack West, MDSwedish Cancer Institute

Seattle, WA

#LCSM ChatMay 26, 2016

8 PM ET/5 PM PT

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Multikinase inhibitor vandetinib to treat RET fusion-positive advanced NSCLC

Abstract #9012, Seto & colleagues

• RET fusion is a recently identified potential driver of NSCLC, seen in 1-2% of cases

• Vandetinib is “multikinase inhibitor” of several targets, incl RET

• Test of vandetinib 300 mg daily in RET fusion+ NSCLC

• Screening of >1500 Japanese pts: 34 (2%) w/RET fusions

• 19 enrolled, 17 w/efficacy data available

• Response rate (RR) 53% and median progression-free surv (PFS) 4.3 mo; of pts w/specific RET fusion (CCDC6-RET), RR 83% (5/6 pts); median PFS 8.3 months

• A promising agent for another rare molecular subgroup

PD-L1 inhibitor avelumab in malignant pleural mesothelioma (MPM)

Abstract #8503, Hassan & colleagues

• Does immune checkpoint inhibitor therapy have significant activity in unresectable MPM?

• 53 patients w/MPM, 81% w/epithelioid subtype• No requirement for threshold PD-L1 expression• Response rate (RR) & progression-free surv (PFS) assessed

• RR 9.4% (5/53), stable disease in 47.2%• Median PFS 17 weeks• No surprising side effects

• Modestly encouraging, but commentary following this is called “Immunotherapy: Reality Check”.

Weekly Taxol (paclitaxel)/Avastin (bevacizumab) vs. Taxotere (docetaxel) in 2nd/3rd Line NSCLC

Abstract #9005, Cortot & colleagues

• Is combination of weekly Taxol/Avastin (Taxol 3 weeks out of 4, Avastin every 2 weeks) superior to Taxotere every 3 weeks as 2nd or 3rd line therapy for advanced NSCLC?

• 166 pts randomized, 2/3 to Taxol/Avastin, 1/3 to Taxotere• 30% had received prior Avastin• Progression-free survival (PFS) was primary endpoint

• Significantly superior PFS (median 5.4 vs. 3.9 mo) & response rate (22.5% vs. 5.5%) for taxol/bev; no better surv

• Far less hematologic (blood counts) side effects w/taxol/bev, but neuropathy, hypertension, many other side effects worse w/taxol/bev

• A promising option for some, but not enough to change std Rx

Daily vs. twice daily (“hyperfractionated”) chest radiation with chemo for limited disease SCLC

Abstract #8504, Faivre-Finn & colleagues

• A study published in the New England Journal of Medicine (Turrisi, 1999) found better survival with twice daily chest radiation combined with cisplatin/etoposide chemo

• This twice daily RT schedule has not been widely adopted due to practical challenges, concerns for greater side effects, and unequal radiation doses in NEJM paper giving daily RT arm a disadvantage

• Randomized trial of 547 LD-SCLC pts to chemo + equal total chest RT doses delivered once or twice daily

• No significant differences in survival or side effects; both groups have better survival than historical numbers

Tagrisso for Leptomeningeal Carcinomatosis (LM) in EGFR Mutation-Positive Advaced NSCLC

Abstract #9002, Yang & colleagues

• LM is seen in 3-5% of pts w/advanced NSCLC but 2-3x more common in pts with EGFR mut-pos NSCLC

• 1st or 2nd gen EGFR inhibs don’t get across blood-brain barrier well at standard dosing

• Is 3rd gen EGFR inhib Tagrisso (osimertinib) more effective: trial of Tagrisso 160 mg/d (2x std dose) in LM

• 20 pts w/EGFR mut+ NSCLC & LM, most treated for weeks to a few months

• 7/20 show imaging improvement, several also show improvement in neuro Sx, reduction in # of cancer cells in cerebrospinal fluid

• Preliminary, but encouraging results for LMFrom Corbin & Nagpal, JAMA Onc 2016

Comparison of Tissue, Plasma, & Urine Testing for EGFR T790M Trial with Rociletinib

Abstract #9001, Wakelee & colleagues

• T790M is acquired resistance mut’n seen in 50-60% of pts w/EGFR mut’n-pos NSCLC progressing after 1st or 2nd gen EGFR inhibitors. Rociletinib active in T790M+ acq’d resistance.

• How well do molecular testing approaches from plasma and urine work for detecting T790M? Do outcomes in patients with T790M detected in plasma and/or urine respond the same as those patients with T790M detected from tissue.

• Plasma & urine detected T790M with sensitivity comparable to that seen w/tissue, which can miss mutations due to tissue heterogeneity; T790M+ pts found by plasma & urine have same response rate & duration of response as T790M+ by tissue.

Local “consolidation” therapy of radiation or surgery after first-line systemic therapy in met NSCLC

Abstract #9004, Gomez & colleagues

• Does local consolidation therapy with radiation or surgery in pts w/up to 3 areas of residual disease after initial chemo or targeted therapy go longer before progressing?

• 254 patients evaluated, 49 randomized to local Rx vs. no• Progression-free survival (PFS) was primary endpoint• Wide range of treatments delivered: surgery, radiation, or

both, at discretion of treating docs• Trial stopped for marked benefit in PFS• But is PFS a useful endpoint if the lesions that would be

progressing have been removed or irradiated? And is this useful if <20% of patients considered get to randomization?

Addition of low molecular weight heparin to adjuvant chemotherapy after surgery for early stage NSCLC 

Abstract #8506, Groen & colleagues

• Does addition of a low-molecular weight heparin during adjuvant chemo improve recurrence-free survival (RFS) in pts with resected early stage NSCLC & getting adjuvant chemo?

• 202 pts randomized to cis/gemcitabine (for squamous NSCLC) or cis/Alimta (pemetrexed) (for non-squamous NSCLC), with or without daily nadroparin under the skin daily x 16 weeks

• Higher neutropenia (low white blood cell count) level w/nadro, but no other differences in side effects

• Median RFS 47.8 vs. 36.1 mo, 3 yr RFS 57% vs. 50%, favoring nadroplatin

• Not likely to change practice yet, but very provocative

Rovalpituzumab tesirine in recurrent or refractory small cell lung cancer (SCLC) 

Abstract #LBA8505, Rudin & colleagues

• Rovalpituzumab tesirine (rova-T) is an “antibody-drug conjugate”, an antibody linked to a chemotherapy agent. The antibody for rova-T is to delta-like protein 3 (DLL3), a marker seen in approximately 70% of SCLC tumors.

• Dr. Cathy Pietanza presented data in 2015 showing a response rate of 23% in previously treated SCLC, but in patients with DLL3-positive SCLC, the response rate was 44%

• No data available yet: this is a “late-breaking abstract”• Among the most promising leads in SCLC; data coming at

ASCO 2016

J-ALEX: Alecensa (Alectinib) vs. Xalkori (Crizotinib) as Initial ALK Inhibitor in ALK+ NSCLC

Abstract #9008, Nokihara & colleagues

• Is 2nd gen ALK inhibitor Alecensa a superior first ALK inhibitor in head to head comparison to Xalkori in pts w/ALK+ met NSCLC?

• 207 patients in open-label randomized trial in Japan• Progression-free survival (PFS) was primary endpoint

• Interim analysis shows highly significant improvement in PFS (median 10.2 months vs. not yet reached), survival immature

• Side effect profile clearly favors Alecensa

• Should this change first line therapy for ALK+ NSCLC?