10 Key ASCO 2014 Presentations in Lung Cancer

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Dr. Jack West offers a list of 10 of the most important, timely abstract presentations in lung cancer, both non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), at the annual ASCO 2014 conference.

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  • Thanks! For better options in treatment, please, visit cancercuremedicine.com, read: http://www.amazon.com/s/ref=nb_sb_noss_1/183-5035389-4416932?url=search-alias%3Daps&field-keywords=travis+christofferson
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  • It's possible that the responders who were T790M-negative were actually T790+ and were 'false negatives'. Others have speculated that they may have just been responding again to a 'rechallenge' with another EGFR TKI, as we sometimes see with other EGFR inhibitors like gefitinib, erlotinib, or afatinib after people have been off of an EGFR inhibitor for a while.
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  • On slide 5 a 23% RR is reported among T790M - . Is it possible that there are positive cells in the body but nog diagnosed because the biopsy can never represent all possible mutated cells ?
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10 Key ASCO 2014 Presentations in Lung Cancer

  1. 1. 10 Key ASCO 2014 Presentations in Lung Cancer: NSCLC and SCLC H. Jack West, MD
  2. 2. • With space to prioritize just 10 key presentations, multiple important trials that have already been reported in press releases as negative were not included. • Trials that provided longer follow up or convey variations of results already presumed or known were not prioritized. • Accordingly, even though there will be several immunotherapy trials with several previously identified and some new immune checkpoint inhibitor agents, none really breaks new ground. Immunotherapy hasn’t lost any momentum, but the story is still being written. Introductory comments on some notable omissions
  3. 3. Tarceva (Erlotinib) +/- Avastin (Bevacizumab) In EGFR Mutation-Positive Adv NSCLC Kato, Abstract #8005 Oral Session, Monday, June 2 154 Japanese EGFR Mutation-Pos Pts, Advanced NSCLC Previously Untreated R A N D Tarceva 150 mg by mouth daily Tarceva 150 mg by mouth daily + Avastin 15 mg/kg IV every 3 weeks • Key results: – Median PFS* 16.0 mo w/combo vs. 9.7 mo for Tarceva (HR^ = 0.54) – Differences by EGFR mutation subtype • Exon 19: Median PFS 18.0 vs. 10.3 mo • Exon 21: Median PFS 13.9 vs. 7.1 mo • Overall Survival not reported, but remarkable improvement in PFS for Tarceva/Avastin in EGFR Mut+ NSCLC, & differences between exon 19 and exon 21 mutations *Progression-Free Survival ^Hazard Ratio
  4. 4. Combined Analysis of Afatinib vs. Chemo in EGFR Mutation-Positive Adv NSCLC • Pooled analysis shows significantly longer overall survival benefit with afatinib, 27.3 vs. 24.3 mo (HR = 0.81) • OS benefit with afatinib is actually seen entirely in exon 19 patients (HR 0.59), while there is actually no benefit (and trend in detrimental direction) in exon 21 patients (HR 1.25) Yang, Abstract #8004 Metastatic NSCLC Oral Session, Monday, June 2 631 pts w/exon 19 or 21 EGFR mut’n, combined from 2 trials (LUX-Lung-3, LUX-Lung-6) R A N D Cisplatin/Pemetrexed (LUX-Lung-3) or Cisplatin/Gemcitabine (LUX-Lung-6) Afatinib 40 mg by mouth
  5. 5. AZD9291 for EGFR Mutation-Positive Patients with Acquired Resistance to EGFR TKI Therapy Janne, Abstract #8009 Clinical Science Symposium, Saturday, May 31 199 EGFR Mut’n-Pos Pts, Advanced NSCLC Prior Progression on EGFR Tyrosine Kinase Inhibitor (TKI) 132 w/centrally confirmed T790M mutation status Dose escalation of oral AZD9291 from 20-240 mg/d 57 Rx’d with free base formulation up to 900 mg 2x/d 31 Rx’d with HBr formulation to to 1000 mg 2x/d 10 transitioned from free base to HBr formulation • RR 51% among 177 evaluable patients, including brain metastases – responses lasting up to 8 months and ongoing • RR 64% among T790M+, 23% among T790M- • Most side effects grade 1: diarrhea, rash, nausea, though 5 cases of interstitial lung disease (ILD) being evaluated
  6. 6. Sequist, Abstract #8010 Clinical Science Symposium, Saturday, May 29 88 EGFR Mut’n Pos Pts, Advanced NSCLC Prior progression on EGFR TKI 2/3 have T790M mutation Dose escalation of CO1686 twice daily 57 Rx’d with free base formulation up to 900 mg 2x/d 31 Rx’d with HBr formulation to to 1000 mg 2x/d 10 transitioned from free base to HBr formulation CO1686 for EGFR Mutation-Positive Patients with Acquired Resistance to EGFR TKI Therapy • Optimal dosing selected as 750 mg HBr, which was 3-fold higher exposure to drug than free base formulation • Leading side effects were nausea, fatigue, and high blood sugar (each in 20-25% of patients) • Responses seen in T790M+ pts treated w/free base 900 mg 2x/d • Responses being seen w/free base, but most too early
  7. 7. Camidge, Abstract #8001 16 patients w/adv NSCLC enrolled, limited to 13 positive for c-MET amplification by FISH (1 low; 6 intermed; 6 high) Crizotinib 250 mg by mouth twice daily Continue until disease progression or prohibitive side effects Metastatic NSCLC Oral Session, Monday, June 2 • XALKORI was originally developed as MET inhibitor but was diverted as “accidental” ALK inhibitor XALKORI (Crizotinib) for c-MET-Positive Advanced NSCLC • Among 12 patients evaluable for response, 4 responses (33%) – 0 of 1 low, 1 (20%) w/intermediate, 3 (50%) w/high amplification • Median duration of response 35 weeks (8 months) • Most common side effects: diarrhea (50%), nausea (31%), vomiting (31%), peripheral edema (25%) visual impairment (25%).
  8. 8. Perol, Abstract #LBA8007 Metastatic NSCLC Oral Session, Monday, June 2 ~1200 pts with adv NSCLC, Squamous & non- squamous Prior platinum-doublet chemo R A N D Taxotere (docetaxel) IV every 3 weeks & Ramucirumab IV every 3 weeks Taxotere (docetaxel) IV every 3 weeks & Placebo IV every 3 weeks • Ramucirumab, now marketed as Cyramza for gastric cancer, is an anti-angiogenic monoclonal antibody inhibitor of VEGF-R2 (similar to Avastin) • Late-breaking abstract, so no details yet provided, but press release in February reports trial is positive for significant progression-free and overall survival benefit • Positive result of targeted therapy combined with second line chemo; also a rare positive trial for pts. w/squamous NSCLC Ramucirumab for Second Line Treatment of Advanced NSCLC: The REVEL Trial
  9. 9. SQUIRE Trial: Necitumumab + Cis/Gem Chemo Leads to Survival Benefit in Squamous NSCLC • Necitumumab is humanized anti-EGFR monoclonal antibody (same mechanism of action as Erbitux (cetuximab)) Thatcher, Abstract #8008 Metastatic NSCLC Oral Session, Monday, June 2 1093 pts advanced Squamous NSCLC Previously untreated R A N D Cisplatin/Gemcitabine every 3 wks x 6 & Necitumumab d1,8 IV every 3 wks Cisplatin/Gemcitabine every 3 wks x 6 • Statistically significant (but not necessarily clinically significant) improvement in overall survival, progression-free survival Necitumumab until progression • Absolute differences: median OS 11.5 vs. 9.9 mo; median OS 5.7 vs. 5.5 months, Response rate 31% vs. 29%
  10. 10. Prophylactic Cranial Irradiation (PCI) for Resected Stage IIIA N2 NSCLC • Closed early due to slow accrual • Disease-free survival (DFS) significantly favors PCI: – Median DFS 28.5 vs. 21.2 mo (HR 0.67, p = 0.37); – 5 yr DFS 29.8 vs 18.5% • 5 yr brain relapse rate 13.6 vs. 41.3% (P<0.0001) • Median OS 31.2 vs. 27.4 mo (NS) • PCI Side effects: nausea, headache, fatigue, usually mild • Small numbers, but huge differences Wang, Abstract #7508 Stage I-III NSCLC & SCLC Poster Highlights Session, Sunday, June 1 156 pts w/resected st IIIA N2 NSCLC, rec’d post-op chemo No evidence of disease R A N D Observation PCI (30 Gy over 10 fractions)
  11. 11. Seto, Abstract #7503 Stage I-III NSCLC & SCLC Oral Session, Monday, June 2 Planned enrollment of 330 pts w/ES-SCLC and any response to first line chemotherapy Stopped early, after 163 pts After futility analysis R A N D Observation PCI (25 Gy over 10 fractions) • PCI led to survival benefit in European trial of patients with ES- SCLC, but no brain imaging done before study entry • Was benefit actually from treating brain metastases? • Though PCI significantly reduced risk of brain metastases (58% vs. 32.4% at 12 mo, p < 0.001), it was associated with a 38% decline in survival (median OS 10.1 vs. 15.1 mo) vs. observation Harmful Effect of Prophylactice Cranial Irradiation (PCI) for Extensive-Stage (ES-)SCLC
  12. 12. “Consolidation” Thoracic Radiation Therapy (TRT) for Residual Chest Disease in ES-SCLC • All patients also received PCI Slotman, Abstract #7502 498 pts with ES-SCLC Any response after 4-6 cycles chemo R A N D Observation Thoracic Radiation Therapy (30 Gy over 10 fractions) • Significant improvement in prog-free survival (HR 0.73, p = 0.001). • Overall survival curves overlap for first 9 months, then separate to favor TRT; no difference in 1 yr survival, but 2 year survival diff is 13% vs. 3% (p = 0.004) • Given results on PCI for ED-SCLC in Japan (Seto abstract), would survival have been better without PCI given to all patients? Stage I-III NSCLC & SCLC Oral Session, Monday, June 2 88% had residual thoracic disease
  13. 13. For questions, comments, and further information, check out CancerGRACE.org

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