- Email: [email protected]
C1-04: A phase II study of RAD001 (everolimus) monotherapy in patients with advanced non-small cell lung cancer (NSCLC) failing prior platinum-based chemotherapy (C) or prior C and EGFR inhibitors (EGFR-I)
Journal of Thoracic Oncology • Volume 2, Number 8, Supplement 4, August 2007
Conclusions: In this randomized Phase II trial of 1st-line advanced NSCLC, vandetanib + CP met the primary endpoint of prolonging PFS vs CP but did not provide a detectable survival advantage. Treatment options with vandetanib in 1st-line NSCLC continue to be explored, and Phase III evaluation of vandetanib in advanced, previously treated NSCLC is ongoing. C1-03
Molecular Targeted Therapy: Beyong EGFR, Wed, 10:30 - 12:15
A phase III randomised, double blind, placebo controlled trial of gemcitabine/carboplatin with or without thalidomide in advanced non-small cell lung cancer (NSCLC)
Lee, Siow-Ming1 Woll, Penella J.2 Rudd, Robin M.3 Gower, Nicole H.4 Ottensmeier, Christian H.5 Ali, Kulsam4 Spiro, Stephen G.1 Hackshaw, Allan4 1 University College London Hospitals NHS Trust, London, UK 2 University of Sheffield, Sheffield, UK 3 London Lung Cancer Group, London, UK 4 University College London, London, UK 5 University of Southampton, Southampton, UK Background: We hypothesised that thalidomide, an oral anti-angiogenic agent with tumour vasculature stabilising, anti-cachexic and immuno-modulatory properties, when combined with chemotherapy and as maintenance treatment would improve survival in patients with stage IIIb or IV NSCLC. Thalidomide has already been shown to be effective in treating myeloma. Here, we present the preliminary findings of the largest phase III trial of thalidomide conducted in NSCLC to date. Methods: Chemo-naive patients with pathologically proven NSCLC, Stage IIIb or IV disease and ECOG performance status (PS) 0-2 were entered into a double-blind placebo-controlled trial from 66 centres in the UK. Patients had adequate renal and haematologic function for platinum based treatment and an estimated life expectancy of greater than 8 weeks. All patients received up to 4 cycles of Gemcitabine 1200 mg/m2 IV (days 1 & 8 of 21 day cycle) and Carboplatin AUC 5 (day 1). Patients were randomised to receive placebo or thalidomide taken orally from the start of chemotherapy and then daily for up to 2 years. The thalidomide/placebo dose began at 100mg/day during chemotherapy. If the patient was able to tolerate this dose, it was increased to 150mg/day after the last chemotherapy cycle for one month, then to 200mg/day for the rest of the trial. Strict guidelines were given regarding pregnancy testing and contraceptive measures. The study end-points were overall survival, time to disease progression, response rates, toxicity and quality of life. The trial had 80% power to show a difference in the overall survival rate at 2 years of 7% (from 12 to 19%). Results: Between 2003 and 2006, 722 patients were randomized (placebo n=350; thalidomide n =372). The median age was 63 yrs (range 33-84 ); 64% were male; main histological subtypes were adenocarcinoma (36%) and squamous cell carcinoma (32%); 44% had stage IIIB and 56% had stage IV disease; and majority had good performance status (ECOG score of 0 and 1 were 31%, 59% respectively). Baseline patient characteristics were well balanced between the arms. The proportions of patients completing all 4 intended chemotherapy cycles were 67% (placebo) and 65% (thalidomide), and the proportions of patients who had their chemotherapy dose delayed or reduced were similar between the trial arms. At the time of this analysis the median follow-up in all patients was 18 months and 620 had died (295 placebo and 325 thalidomide), of which 90% were reported to have died from lung cancer. There was no evidence of a difference in overall survival. The median survival was 8.9 months (placebo) and 8.4 months
Copyright © 2007 by the International Association for the Study of Lung Cancer
12th World Conference on Lung Cancer
(thalidomide). The hazard ratio was 1.13 (95% CI 0.96 to 1.32), p=0.14 from a logrank test. The 2-year survival rate was 14% and 10% in the placebo and thalidomide arms respectively. Subgroup analyses based on gender, age, performance status, tumour stage and cell type did not provide any evidence of a beneficial effect of thalidomide for any of these factors. The results on progression-free survival were consistent with those on overall survival, and again showed no survival effect of using thalidomide. The main adverse effect associated with thalidomide was a thrombotic event and this was easily treated with anti-coagulants. 117 patients experienced at least one such event (mainly pulmonary embolus and deep vein thrombosis) with 20% in the thalidomide arm compared to 12% on placebo - relative risk of 1.68 (95% CI 1.19 to 2.38). There was no statistically significant difference in haematological toxicities, 40% (placebo) vs 43% (thalidomide), or non-haematological toxicities (excluding thrombotic events), 16% (placebo) vs 19% (thalidomide). Conclusions - Preliminary analyses demonstrated that thalidomide in combination with gemcitabine and carboplatin and as maintenance treatment in chemotherapy-naive NSCLC patients did not improve survival and progression-free survival over gemcitabine and carboplatin alone and was associated with increased thrombotic events. The final analyses, including those on quality of life and response rates, will be presented for both treatment groups. C1-04
Molecular Targeted Therapy: Beyong EGFR, Wed, 10:30 - 12:15
A phase II study of RAD001 (everolimus) monotherapy in patients with advanced non-small cell lung cancer (NSCLC) failing prior platinum-based chemotherapy (C) or prior C and EGFR inhibitors (EGFR-I)
Papadimitrakopoulou, Vassiliki1 Soria, Jean-Charles2 Douillard, JeanYves3 Giaccone, Giuseppe4 Wolf, Jürgen5 Crino, Lucio6 Cappuzzo, Federico7 Sharma, Sunil8 Gross, Stefan H.9 Shepherd, Frances A.10 1 MD Anderson Cancer Center, Houston, TX, USA 2 Institute Gustave Roussy, Villejuif, France 3 Centre Rene Gauducheau, St. Herblain, France 4 VU Medical Center, Amsterdam, The Netherlands 5 University Hospital, Cologne, Germany 6 Ospedale Silvestrini, Perugia, Italy 7 Instituto Clinico Humanitas, Milano, Italy 8 Nevada Cancer Center, Las Vesgas, NV, USA 9 Novartis Oncology, Basel, Switzerland 10 Princess Margaret Hospital, Toronto, ON, Canada Background: RAD001®, an oral inhibitor of the mammalian target of rapamycin (mTOR) that has shown anti-tumor activity both as singleagent and in combination with other anticancer agents in in vitro and in vivo NSCLC models. In a phase I study, 4 disease stabilizations (SD) and 1 partial response (PR) as per RECIST were reported from 14 NSCLC pts treated with R monotherapy. Methods: Advanced NSCLC pts with adequate organ function, performance status ≤ 2, failing either ≤ 2 C (arm 1) or ≤ 2 C and an EGFR-I (arm 2) were treated with R at 10 mg qd if tolerable until progression (PD). The study applied a Simon-2-stage design with primary endpoint of objective tumor response rate (RR) according to RECIST. CT scans were performed every 28 days until month 4 and then every 2 months thereafter. Adverse events (AE) were assessed using NCI CTC v.3.0. Biomarker analysis was performed on tumor tissues. Results: This analysis is based on data acquired up to 20Sep2006. 85 pts were enrolled between Aug 2005 and May 2006. Demographics and patient disposition were (arm 1/arm 2): 42/43 (7 pts ongoing), female 38.1%/51.2%, never smoker 14.3%/44.2%, adenoca. 57.1%/62.8%,
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Journal of Thoracic Oncology • Volume 2, Number 8, Supplement 4, August 2007
squamous cell ca. 21.4%/14.0%, BAC 2.4%/16.3%, others 19.1%/6.9%. Median age was 60 years (range 21-74). R was given on arm 1 as 2nd line therapy in 64.3% of pts., as 3rd line in 35.7% and on arm 2 as 3rd line in 58.1%, as 4th line in 41.9%. 90.6% pts had stage IV disease. The trial did not proceed to stage 2 based on RR for 74 pts in the efficacy population. Best overall tumor response (arm 1/2 in %): confirmed PR (5.3/2.8) and SD (44.7/44.4). Median PFS is 11.3 weeks (95% CI: 8.1; 12.4) in arm 1 and 9.7 weeks (7.3; 13.0) in arm 2. Out of 42 (arm 1) and 43 (arm 2) patients in the intent-to-treat population, 22 and 17 respectively achieved a best overall response of SD or better (CR+PR): in arm 1 duration of SD observed at the cut-off date ranged from 49 days (censored) to 267 days (8 pts have duration of SD>3 months) and in arm 2 from 68 to 231 days (11 pts have duration of SD>3 months). Most frequent AEs (pts, all grades/grade 3&4): stomatitis/mucositis (43/5), cough (27/1), dyspnea (33/8), rash (26/0), fatigue (25/10), anorexia (25/1), nausea (20/0), anemia (18/3), epistaxis (18/0), diarrhea (17/2). IHC analyses of tumor tissue samples confirmed that high levels of pEGFR correlate with activation (upregulation) of the p-AKT. Detailed analyses will be presented. Conclusions: 10 mg qd R monotherapy is well tolerated and shows limited activity in pretreated advanced NSCLC pts with respect to response. R effect in disease control has to be further investigated. Combination trials with both standard chemotherapy and targeted agents are ongoing. C1-05
12th World Conference on Lung Cancer
14-week cycles (12 weeks on, 2 weeks off), in a centrally monitored trial. The primary endpoint was overall survival (OS) with 80% power to detect an improvement in median OS with a 1-tailed α=0.05. Results: All patients had previously received a 1st line platinum based regimen; 25 also received 2nd line therapy. The TLF and placebo arms enrolled 47 and 53 patients, respectively. Baseline characteristics were similar in both groups, including proportion of patients receiving 1 or 2 prior regimens. All patients were included in the Intent To Treat (ITT) analysis. The trial met its primary endpoint with a 62% increase in median OS (2.3 months; HR 0.69; p<0.05). The talactoferrin effect was also seen in relevant subsets, including patients with Stage IIIB or IV disease, ECOG 0 or 1, or one/two prior therapies. TLF was well tolerated; adverse events (AEs) were generally mild. No drug-related serious AEs were reported, and the incidence of total AEs and Grade 3/4 AEs was similar in both arms. Conclusion: Oral talactoferrin, a promising new anti-cancer agent, significantly improved survival in patients with refractory NSCLC in this randomized, placebo-controlled trial. TLF was well tolerated in this population. Given its favorable toxicity profile, TLF may be particularly attractive in refractory patients with poor performance status.
Molecular Targeted Therapy: Beyong EGFR, Wed, 10:30 - 12:15
Oral talactoferrin extends survival in patients with refractory NSCLC in a randomized, placebo-controlled, phase 2 trial
Parikh, Purvish M.1 Wang, Yenyun2 Ranade, A. A.3 Vaid, A. K.4 Advani, S. H.5 Raghunadharao, D.6 Nag, S.7 Madhavan, J. P.8 Varadhachary, Atul9 1 Tata Memorial Hospital, Mumbai, India 2 Agennix Inc., Houston, TX, USA 3 Deenanath Mangeshkar Hospital, Pune, India 4 Rajeev Gandhi Cancer Institute, Delhi, India 5 Jaslok Hospital, Mumbai, India 6 Nizam’s Institute, Hyderabad, India 7 Jehangir Hospital, Pune, India 8 Regional Cancer Center, Trivandrum, India 9 Agennix, Inc., Houston, TX, USA Background: Talactoferrin alfa (TLF), an orally active immunomodulatory protein, acts at the gut through a novel mechanism of action. In animal experiments, TLF bound enterocyte receptors and immune cells in the Peyer’s patches, induced DC maturation, and initiated an immunostimulatory cascade in the Gut Associated Lymphoid Tissue (GALT), with activation of innate and adaptive immunity. GALT immunomodulation was followed by systemic increases in NK and CTL activity, activation of tumor-draining lymph nodes, and cellular infiltration of distant tumors. Talactoferrin showed anti-cancer activity in preclinical experiments and in non-small cell lung cancer (NSCLC) patients in Phase 1b studies. Two randomized, placebo-controlled Phase 2 NSCLC studies were conducted with TLF as a single agent and combined with carboplatin and paclitaxel. The 110-patient combination therapy study (previously presented) met its primary endpoint with an improved overall response over chemotherapy alone. We now present results from the placebo-controlled single agent study. Methods: 100 Stage IIIB/IV NSCLC patients who had progressed after first- or second-line therapy were enrolled at 10 leading Indian cancer centers, and randomized to receive supportive care plus either oral TLF (1.5 g bid) or placebo. TLF/placebo was administered, for up to three
S360
Figure. Kaplan Meier Curves (Months)
C1-06
Molecular Targeted Therapy: Beyong EGFR, Wed, 10:30 - 12:15
BO17704: a phase III study of first-line cisplatin and gemcitabine with bevacizumab or placebo in patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC)
Reck, Martin1 von Pawel, Joachim2 Zatloukal, Petr3 Ramlau, Rodryg4 Gorbounova, Vera5 Hirsh, Vera6 Leighl, Natasha7 Mezger, Jörg8 Archer, Venice9 Manegold, Christian10 1 Hospital Grosshansdorf, Grosshansdorf, Germany 2 Asklepios Klinikum Gauting, Muenchen-Gauting, Germany 3 Faculty Hospital Bulovka, Prague, Czech Republic 4 Wielkopolskie Centrum Chorob Pluc i Gruzlicy, Poznan, Poland 5 Cancer Research Center, Moscow, Russia 6 MUHC - Royal Victoria Hospital, Montreal, QC, Canada 7 Princess Margaret Hospital, Toronto, ON, Canada 8 St. Vincentius-Kliniken, Karlsruhe, Germany 9 F. Hoffmann-La Roche, Basel, Switzerland 10 University Medical Centre, Mannheim, Germany
Copyright © 2007 by the International Association for the Study of Lung Cancer
Conclusions: In this randomized Phase II trial of 1st-line advanced NSCLC, vandetanib + CP met the primary endpoint of prolonging PFS vs CP but did not provide a detectable survival advantage. Treatment options with vandetanib in 1st-line NSCLC continue to be explored, and Phase III evaluation of vandetanib in advanced, previously treated NSCLC is ongoing. C1-03
Molecular Targeted Therapy: Beyong EGFR, Wed, 10:30 - 12:15
A phase III randomised, double blind, placebo controlled trial of gemcitabine/carboplatin with or without thalidomide in advanced non-small cell lung cancer (NSCLC)
Lee, Siow-Ming1 Woll, Penella J.2 Rudd, Robin M.3 Gower, Nicole H.4 Ottensmeier, Christian H.5 Ali, Kulsam4 Spiro, Stephen G.1 Hackshaw, Allan4 1 University College London Hospitals NHS Trust, London, UK 2 University of Sheffield, Sheffield, UK 3 London Lung Cancer Group, London, UK 4 University College London, London, UK 5 University of Southampton, Southampton, UK Background: We hypothesised that thalidomide, an oral anti-angiogenic agent with tumour vasculature stabilising, anti-cachexic and immuno-modulatory properties, when combined with chemotherapy and as maintenance treatment would improve survival in patients with stage IIIb or IV NSCLC. Thalidomide has already been shown to be effective in treating myeloma. Here, we present the preliminary findings of the largest phase III trial of thalidomide conducted in NSCLC to date. Methods: Chemo-naive patients with pathologically proven NSCLC, Stage IIIb or IV disease and ECOG performance status (PS) 0-2 were entered into a double-blind placebo-controlled trial from 66 centres in the UK. Patients had adequate renal and haematologic function for platinum based treatment and an estimated life expectancy of greater than 8 weeks. All patients received up to 4 cycles of Gemcitabine 1200 mg/m2 IV (days 1 & 8 of 21 day cycle) and Carboplatin AUC 5 (day 1). Patients were randomised to receive placebo or thalidomide taken orally from the start of chemotherapy and then daily for up to 2 years. The thalidomide/placebo dose began at 100mg/day during chemotherapy. If the patient was able to tolerate this dose, it was increased to 150mg/day after the last chemotherapy cycle for one month, then to 200mg/day for the rest of the trial. Strict guidelines were given regarding pregnancy testing and contraceptive measures. The study end-points were overall survival, time to disease progression, response rates, toxicity and quality of life. The trial had 80% power to show a difference in the overall survival rate at 2 years of 7% (from 12 to 19%). Results: Between 2003 and 2006, 722 patients were randomized (placebo n=350; thalidomide n =372). The median age was 63 yrs (range 33-84 ); 64% were male; main histological subtypes were adenocarcinoma (36%) and squamous cell carcinoma (32%); 44% had stage IIIB and 56% had stage IV disease; and majority had good performance status (ECOG score of 0 and 1 were 31%, 59% respectively). Baseline patient characteristics were well balanced between the arms. The proportions of patients completing all 4 intended chemotherapy cycles were 67% (placebo) and 65% (thalidomide), and the proportions of patients who had their chemotherapy dose delayed or reduced were similar between the trial arms. At the time of this analysis the median follow-up in all patients was 18 months and 620 had died (295 placebo and 325 thalidomide), of which 90% were reported to have died from lung cancer. There was no evidence of a difference in overall survival. The median survival was 8.9 months (placebo) and 8.4 months
Copyright © 2007 by the International Association for the Study of Lung Cancer
12th World Conference on Lung Cancer
(thalidomide). The hazard ratio was 1.13 (95% CI 0.96 to 1.32), p=0.14 from a logrank test. The 2-year survival rate was 14% and 10% in the placebo and thalidomide arms respectively. Subgroup analyses based on gender, age, performance status, tumour stage and cell type did not provide any evidence of a beneficial effect of thalidomide for any of these factors. The results on progression-free survival were consistent with those on overall survival, and again showed no survival effect of using thalidomide. The main adverse effect associated with thalidomide was a thrombotic event and this was easily treated with anti-coagulants. 117 patients experienced at least one such event (mainly pulmonary embolus and deep vein thrombosis) with 20% in the thalidomide arm compared to 12% on placebo - relative risk of 1.68 (95% CI 1.19 to 2.38). There was no statistically significant difference in haematological toxicities, 40% (placebo) vs 43% (thalidomide), or non-haematological toxicities (excluding thrombotic events), 16% (placebo) vs 19% (thalidomide). Conclusions - Preliminary analyses demonstrated that thalidomide in combination with gemcitabine and carboplatin and as maintenance treatment in chemotherapy-naive NSCLC patients did not improve survival and progression-free survival over gemcitabine and carboplatin alone and was associated with increased thrombotic events. The final analyses, including those on quality of life and response rates, will be presented for both treatment groups. C1-04
Molecular Targeted Therapy: Beyong EGFR, Wed, 10:30 - 12:15
A phase II study of RAD001 (everolimus) monotherapy in patients with advanced non-small cell lung cancer (NSCLC) failing prior platinum-based chemotherapy (C) or prior C and EGFR inhibitors (EGFR-I)
Papadimitrakopoulou, Vassiliki1 Soria, Jean-Charles2 Douillard, JeanYves3 Giaccone, Giuseppe4 Wolf, Jürgen5 Crino, Lucio6 Cappuzzo, Federico7 Sharma, Sunil8 Gross, Stefan H.9 Shepherd, Frances A.10 1 MD Anderson Cancer Center, Houston, TX, USA 2 Institute Gustave Roussy, Villejuif, France 3 Centre Rene Gauducheau, St. Herblain, France 4 VU Medical Center, Amsterdam, The Netherlands 5 University Hospital, Cologne, Germany 6 Ospedale Silvestrini, Perugia, Italy 7 Instituto Clinico Humanitas, Milano, Italy 8 Nevada Cancer Center, Las Vesgas, NV, USA 9 Novartis Oncology, Basel, Switzerland 10 Princess Margaret Hospital, Toronto, ON, Canada Background: RAD001®, an oral inhibitor of the mammalian target of rapamycin (mTOR) that has shown anti-tumor activity both as singleagent and in combination with other anticancer agents in in vitro and in vivo NSCLC models. In a phase I study, 4 disease stabilizations (SD) and 1 partial response (PR) as per RECIST were reported from 14 NSCLC pts treated with R monotherapy. Methods: Advanced NSCLC pts with adequate organ function, performance status ≤ 2, failing either ≤ 2 C (arm 1) or ≤ 2 C and an EGFR-I (arm 2) were treated with R at 10 mg qd if tolerable until progression (PD). The study applied a Simon-2-stage design with primary endpoint of objective tumor response rate (RR) according to RECIST. CT scans were performed every 28 days until month 4 and then every 2 months thereafter. Adverse events (AE) were assessed using NCI CTC v.3.0. Biomarker analysis was performed on tumor tissues. Results: This analysis is based on data acquired up to 20Sep2006. 85 pts were enrolled between Aug 2005 and May 2006. Demographics and patient disposition were (arm 1/arm 2): 42/43 (7 pts ongoing), female 38.1%/51.2%, never smoker 14.3%/44.2%, adenoca. 57.1%/62.8%,
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Journal of Thoracic Oncology • Volume 2, Number 8, Supplement 4, August 2007
squamous cell ca. 21.4%/14.0%, BAC 2.4%/16.3%, others 19.1%/6.9%. Median age was 60 years (range 21-74). R was given on arm 1 as 2nd line therapy in 64.3% of pts., as 3rd line in 35.7% and on arm 2 as 3rd line in 58.1%, as 4th line in 41.9%. 90.6% pts had stage IV disease. The trial did not proceed to stage 2 based on RR for 74 pts in the efficacy population. Best overall tumor response (arm 1/2 in %): confirmed PR (5.3/2.8) and SD (44.7/44.4). Median PFS is 11.3 weeks (95% CI: 8.1; 12.4) in arm 1 and 9.7 weeks (7.3; 13.0) in arm 2. Out of 42 (arm 1) and 43 (arm 2) patients in the intent-to-treat population, 22 and 17 respectively achieved a best overall response of SD or better (CR+PR): in arm 1 duration of SD observed at the cut-off date ranged from 49 days (censored) to 267 days (8 pts have duration of SD>3 months) and in arm 2 from 68 to 231 days (11 pts have duration of SD>3 months). Most frequent AEs (pts, all grades/grade 3&4): stomatitis/mucositis (43/5), cough (27/1), dyspnea (33/8), rash (26/0), fatigue (25/10), anorexia (25/1), nausea (20/0), anemia (18/3), epistaxis (18/0), diarrhea (17/2). IHC analyses of tumor tissue samples confirmed that high levels of pEGFR correlate with activation (upregulation) of the p-AKT. Detailed analyses will be presented. Conclusions: 10 mg qd R monotherapy is well tolerated and shows limited activity in pretreated advanced NSCLC pts with respect to response. R effect in disease control has to be further investigated. Combination trials with both standard chemotherapy and targeted agents are ongoing. C1-05
12th World Conference on Lung Cancer
14-week cycles (12 weeks on, 2 weeks off), in a centrally monitored trial. The primary endpoint was overall survival (OS) with 80% power to detect an improvement in median OS with a 1-tailed α=0.05. Results: All patients had previously received a 1st line platinum based regimen; 25 also received 2nd line therapy. The TLF and placebo arms enrolled 47 and 53 patients, respectively. Baseline characteristics were similar in both groups, including proportion of patients receiving 1 or 2 prior regimens. All patients were included in the Intent To Treat (ITT) analysis. The trial met its primary endpoint with a 62% increase in median OS (2.3 months; HR 0.69; p<0.05). The talactoferrin effect was also seen in relevant subsets, including patients with Stage IIIB or IV disease, ECOG 0 or 1, or one/two prior therapies. TLF was well tolerated; adverse events (AEs) were generally mild. No drug-related serious AEs were reported, and the incidence of total AEs and Grade 3/4 AEs was similar in both arms. Conclusion: Oral talactoferrin, a promising new anti-cancer agent, significantly improved survival in patients with refractory NSCLC in this randomized, placebo-controlled trial. TLF was well tolerated in this population. Given its favorable toxicity profile, TLF may be particularly attractive in refractory patients with poor performance status.
Molecular Targeted Therapy: Beyong EGFR, Wed, 10:30 - 12:15
Oral talactoferrin extends survival in patients with refractory NSCLC in a randomized, placebo-controlled, phase 2 trial
Parikh, Purvish M.1 Wang, Yenyun2 Ranade, A. A.3 Vaid, A. K.4 Advani, S. H.5 Raghunadharao, D.6 Nag, S.7 Madhavan, J. P.8 Varadhachary, Atul9 1 Tata Memorial Hospital, Mumbai, India 2 Agennix Inc., Houston, TX, USA 3 Deenanath Mangeshkar Hospital, Pune, India 4 Rajeev Gandhi Cancer Institute, Delhi, India 5 Jaslok Hospital, Mumbai, India 6 Nizam’s Institute, Hyderabad, India 7 Jehangir Hospital, Pune, India 8 Regional Cancer Center, Trivandrum, India 9 Agennix, Inc., Houston, TX, USA Background: Talactoferrin alfa (TLF), an orally active immunomodulatory protein, acts at the gut through a novel mechanism of action. In animal experiments, TLF bound enterocyte receptors and immune cells in the Peyer’s patches, induced DC maturation, and initiated an immunostimulatory cascade in the Gut Associated Lymphoid Tissue (GALT), with activation of innate and adaptive immunity. GALT immunomodulation was followed by systemic increases in NK and CTL activity, activation of tumor-draining lymph nodes, and cellular infiltration of distant tumors. Talactoferrin showed anti-cancer activity in preclinical experiments and in non-small cell lung cancer (NSCLC) patients in Phase 1b studies. Two randomized, placebo-controlled Phase 2 NSCLC studies were conducted with TLF as a single agent and combined with carboplatin and paclitaxel. The 110-patient combination therapy study (previously presented) met its primary endpoint with an improved overall response over chemotherapy alone. We now present results from the placebo-controlled single agent study. Methods: 100 Stage IIIB/IV NSCLC patients who had progressed after first- or second-line therapy were enrolled at 10 leading Indian cancer centers, and randomized to receive supportive care plus either oral TLF (1.5 g bid) or placebo. TLF/placebo was administered, for up to three
S360
Figure. Kaplan Meier Curves (Months)
C1-06
Molecular Targeted Therapy: Beyong EGFR, Wed, 10:30 - 12:15
BO17704: a phase III study of first-line cisplatin and gemcitabine with bevacizumab or placebo in patients with advanced or recurrent non-squamous non-small cell lung cancer (NSCLC)
Reck, Martin1 von Pawel, Joachim2 Zatloukal, Petr3 Ramlau, Rodryg4 Gorbounova, Vera5 Hirsh, Vera6 Leighl, Natasha7 Mezger, Jörg8 Archer, Venice9 Manegold, Christian10 1 Hospital Grosshansdorf, Grosshansdorf, Germany 2 Asklepios Klinikum Gauting, Muenchen-Gauting, Germany 3 Faculty Hospital Bulovka, Prague, Czech Republic 4 Wielkopolskie Centrum Chorob Pluc i Gruzlicy, Poznan, Poland 5 Cancer Research Center, Moscow, Russia 6 MUHC - Royal Victoria Hospital, Montreal, QC, Canada 7 Princess Margaret Hospital, Toronto, ON, Canada 8 St. Vincentius-Kliniken, Karlsruhe, Germany 9 F. Hoffmann-La Roche, Basel, Switzerland 10 University Medical Centre, Mannheim, Germany
Copyright © 2007 by the International Association for the Study of Lung Cancer