- Email: [email protected]
PS03.03 Salvage Therapy for Relapse after Stereotactic Body Radiation for Stage I Lung Cancer
November 2017 retrospective analysis of the clinico-pathologic features of patients diagnosed with pulmonary carcinoids tumor at the LVHN over a ten year period. Methods: Patients with primary pulmonary carcinoid tumors diagnosed between 2005 and 2015 were identified from tumor registry. Records were de-identified and reviewed. Results: Ninety-six patients with primary pulmonary carcinoid were identified. Median age was 63.5 years. 69% were female and 97% were Caucasian. The most common presenting symptoms were cough (22%), dyspnea (17%), chest pain (11%), pneumonia (9%) and hemoptysis (6%). 56% had no symptoms. 86 patients had typical carcinoids and 10 patients had atypical carcinoids. 75% were stage 1, 5% stage II, 4% stage III and 6% stage IV with metastases to bone, lung and liver. 10% had multifocal pulmonary disease. 90% underwent surgery (62% lobectomy, 20% wedge resection, 4% segmental resection, 4% pneumonectomy and 2% endobronchial ablation). Two patients had concurrent lobectomy and wedge resection. Five patients received chemotherapy, 3 with metastatic disease, 1 with stage IIIA and 1 misdiagnosed small cell lung carcinoma. Chemotherapy regimens involved cisplatin and etoposide in 3 patients, and 2 patients received treatment elsewhere. Three patients received radiation therapy. One had prophylactic cranial irradiation, 1 required palliative radiation for painful bony metastases and 1 received concurrent radiation with chemotherapy. Four patients had disease recurrence, 2 of whom died of metastatic pulmonary carcinoid. Ten patients died during the study period from other causes. Conclusion: Primary pulmonary carcinoids are rare tumors more common in females. Common presenting symptoms are cough, dyspnea, chest pain and pneumonia. Surgery is the mainstay of treatment. Chemotherapy and radiation therapy are rarely used except in the metastatic setting. Keeping with the indolent nature of the disease, most patients die of other causes.
PS03.01 Elective Nodal Irradiation for Limited-Stage Small Cell Lung Cancer: A survey of US Radiation Oncologists on Practices Topic: Radiation Oncology M.J. Farrell,1 J. Yahya,1 C. Degnin,1 Y. Chen,1 J.M. Holland,1 M.A. Henderson,1 J.J. Jaboin,1 M.M. Harkenrider,2 C.R. Thomas Jr.,1 T. Mitin1 1Radiation Medicine, Oregon Health and Science University, Portland, OR/US, 2Stritch School of Medicine, Loyola University Chicago, Chicago, IL/US Background: Elective nodal irradiation (ENI) has traditionally been used in clinical trials that have established thoracic radiotherapy (TRT) as instrumental in improving overall survival in patients with limitedstage small cell lung cancer (LS-SCLC). However, several publications suggest that omission of ENI may be appropriate. The current randomized trial CALGB 30610 mandates elective irradiation of ipsilateral hilar lymph nodes only, while EORTC 08072 (CONVERT) omitted ENI completely. Current US practice patterns are unknown in regards to ENI for patients with LS-SCLC. Methods: We surveyed practicing US radiation oncologists (ROs) via an IRB-approved online questionnaire. Questions covered background characteristics, self-rated knowledge of key trials, and treatment recommendations for LS-SCLC, based on several hypothetical clinical scenarios. Results: We received 309 responses from practicing ROs. Only a minority of respondents recommended ENI for patients with LS-SCLC: 21% for N0 disease, 29% for N1 disease, and 30% for N2 disease. 64% did not recommend ENI in any of these clinical scenarios. Respondents who recommended ENI were more likely to have been practicing over 10 years since residency training (p<0.01), more likely to be in private practice rather than an academic setting (p¼0.04), and less likely to be familiar with the ongoing CALGB 30610 trial (p¼0.04). Almost uniformly, respondents prescribe the same RT dose to the primary disease and involved lymph
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nodes (93%). When delivering ENI, 36% prescribe the same dose to involved and elective nodes, whereas 64% prescribe a lower dose to elective nodes than involved nodes. Conclusion: In our survey of US ROs, 64% of respondents did not recommend ENI. This is a dramatic shift in practice, as a similar survey of ROs conducted in 2007 showed this number to be 18%. Physicians further away from residency training were more likely to recommend ENI. In the recent EORTC 08072 trial, which omitted ENI, overall survival was higher than previously reported and radiation toxicities were lower than expected in both treatment arms, lending further evidence that omitting ENI should be considered a standard treatment strategy at this time. Results from the CALGB 30610 trial with limited ENI will further elucidate the role of ENI. Education of patients and physicians is essential in aligning practice patterns with the best clinical evidence.
PS03.02 Amifostine as a Cytoprotectant in Small Cell Lung Cancer Topic: Radiation Oncology J. Pollock,1 A.E. Pollock2 1Radiation Oncology, The Schiffler Cancer Center, Wheeling, WV/US, 2Radiation Oncology, Schiffler Cancer Center, Wheeling, WV/US Background: Chemoradiotherapy-induced esophagitis remains a dose limiting toxicity experienced by 35% of patients with locally advanced lung cancer. Data has demonstrated a benefit to intravenous amifostine as a means of reducing acute esophagitis in patients receiving concurrent chemoradiotherpay in non-small cell lung cancer, though none have shown an effect in small cell lung cancer. Our center has adopted a subcutaneous injection schedule and we report our retrospective findings. Methods: 49 patients with stage 3 small cell lung cancer received concurrent thoracic chemoradiotherapy. Chemotherapy consisted of cisplatin (120 mg/m2) and etoposide (60 mg/m2) on days 1 and 21 along with conformal radiotherapy (RT) encompassing CT-identified gross tumor volume. Dose delivery was 150 cGy twice daily with a 6 hour inter-treatment interval (total dose 4500 cGy). In 32 patients (group 1), amifostine was delivered (500 mg, sc divided in two injections) prior to the second daily RT fraction on non-chemotherapy days. The remaining 17 patients (group 2) did not receive amifostine due to choice or intolerance of the drug. Results: Metrics of esophagitis included weight loss and opiate requirement. 31% of group 1 required opiates at a median RT dose of 3300 cGy. 42% of group 2 required opiates during treatment at a median dose of 2250 cGy. Other variables evaluated to determine an association between amifostine use and esophagitis included esophageal V20, V30, and V50. No significant relationship was identified. Figure 1 illustrates a later need for opiate use in the amifostine group but this did not reach significance. Conclusion: In this modern retrospective series of thoracic chemoradiotherapy for stage 3 small cell lung cancer, subcutaneous amifostine did not significantly reduce the incidence of esophagitis. Limitations include small sample size and, due to a trend in postponing the onset of esophagitis, our center continues this practice.
PS03.03 Salvage Therapy for Relapse after Stereotactic Body Radiation for Stage I Lung Cancer Topic: Radiation Oncology Z.A. Oaks, J. Bogart, T. Nsouli, P. Aridgides Radiation Oncology, SUNY Upstate, Syracuse, NY/US Background: To evaluate treatment outcomes of recurrent non-small cell lung cancer (NSCLC) following initial SBRT for stage I disease.
S1576 Methods: Retrospective review of patients treated with SBRT for stage I NSCLC from 2007-2017 who were found to have relapsed. Recurrences were classified as local (initial treated lesion), lobar (outside the treated lesion but confined to one lobe), nodal (hilum or mediastinum), or distant. Results: Out of 297 treated with SBRT, 61 patients were found to have recurrence including 5 local, 14 lobar, 18 nodal, and 24 distant. Local recurrences developed at a median 21.2 months (range 11.6-63.4) from SBRT, and salvage treatment included radiation with concurrent chemotherapy (2 patients), lobectomy (2 patients), or radiofrequency ablation (1 patient). Lobar recurrences developed in a median 12 months (1.3 to 44.2), and nodal recurrences developed with median 11.3 months (1.8 to 34.5). Of 7 patients treated definitively after lobar relapse, 6 patients developed subsequent distant or regional relapse. Four of 11 patients treated for nodal relapse were salvaged without subsequent relapse. Approximately 40% of patients with lobar or nodal relapse did not undergo salvage therapy often due to poor functional status. Treatment related grade 3 + toxicity was not reported for patients treated with definitive salvage therapy. Median overall survival was 51 months after local relapse, 16 months after lobar relapse, and 13.7 months after nodal relapse. Median survival was 46 months for patients receiving definitive salvage therapy for intrathoracic recurrence compared with 9.7 months for patients not treated definitively. Distant recurrences occurred with a median of 10.9 months (range 2.0-55.9) after SBRT, and median survival was only 6.2 months after distant relapse in this group. Conclusion: Salvage therapy is feasible in the majority of patients with local or locoregional relapse after SBRT for stage I NSCLC. The success of salvage therapy appears to correlate with site of relapse with an unexpected high rate of subsequent relapse in patients treated for lobar recurrence. Novel approaches should be considered for addressing systemic disease in this poor risk population of patients.
PS03.04 Stereotactic Body Radiation Therapy (SBRT) Experience in Lung Oligometastases Topic: Radiation Oncology P. Antonini, L. Larrea, E. López, V. González, J. Bea, C. Baños Radiation Oncology, Hospital Virgen del Consuelo, Valencia/ES Background: The aim of this study is to review our experience and evaluate the results of SBRT for lung oligometastases in terms of survival, local control and toxicity. Methods: The medical records of all patients treated at single institution between 2002 and 2016 were retrospectively analyzed. There were 102 patients with 136 lung metastases treated with SBRT. Primary tumors included: previously treated non-small cell lung carcinoma (52%), colo-rectal adenocarcinoma (36%), gastroesophageal tumors, melanoma, endometrial cancer, urologic (renal/vesical), thyroid neoplasms (2% each) and unknown primary (4%). All patients had Karnofsky Performance Status > 80% and systemic disease was controlled in 85%. Prior treatments included: chemotherapy (70%) and surgery to primary/metastases (58%). SBRT treatment was delivered with multiple static non-coplanar beams or arc therapy. Prescribed dose was either 45 Gy in 3 fractions or a single 30-Gy fraction, ensuring BEDs>100Gy. Dose constraints were set for spinal cord, lung and esophagus. Toxicity and radiologic response were assessed in follow-up visits, using RTOG-EORTC scores and radiologist reviewed reports (RECIST/OMS criteria). Survival rates and toxicities were estimated using Kaplan-Meier method. Results: Median age was 71 years (28-88), 40% were elderly (>75 years old). Median tumor volume was 5.2 cm3 (0.11-144). Median follow-up was 16 months (377). Overall survival is 89% and 66% at 1 and 2 years. Local control is 99,3%, the only local relapse occurred in neuroendocrine histology. Acute toxicities grade 2 or less occurred in 11 %: esofagitis, dermitis or chest pain. Asymptomatic radiographic neumonitis was detected in 7 %
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of patients. To date, no significant chronic toxicities have been recorded. Conclusion: Our experience includes a significant proportion of elderly patients with controlled systemic disease and good performance status. SBRT appears as an excellent option in lung metastases of various origins, given the encouraging results considering overall survival, local control and reported toxicity.
PS04.01 ADAURA: PhIII, Double-Blind, Randomized Study of Osimertinib vs Placebo in EGFR Mutation-Positive NSCLC Post-Tumor Resection Topic: Medical Oncology R.S. Herbst,1 Y. Wu,2 H. Mann,3 Y. Rukazenkov,3 M. Marotti,3 M. Tsuboi4 1Yale Cancer Center, Yale-New Haven Hospital, New Haven, CT/US, 2Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangzhou/CN, 3AstraZeneca, Cambridge/GB, 4Division of Thoracic Surgery and Oncology, National Cancer Center Hospital East, Chiba/JP Background: EGFR-TKIs are standard first-line therapy in patients with EGFR sensitizing mutation (EGFRm)-positive advanced NSCLC. EGFR T790M resistance mutation is observed in >50% of patients with acquired resistance to EGFR-TKIs. Osimertinib is a third-generation, irreversible, CNS-active EGFR-TKI selective for EGFRm and T790M, recommended in patients with T790M-positive advanced NSCLC who have progressed on first-line EGFR-TKIs. In a recent study (NCT01405079), gefitinib treatment in patients with resected EGFRmpositive NSCLC significantly increased disease-free survival (DFS) vs vinorelbine+cisplatin: median 28.7 vs 18.0 months (hazard ratio 0.60 (95% CI 0.42e0.87), p¼0.005), warranting further investigation of EGFR-TKIs in this setting (Wu et al, J Clin Oncol 2017;35:suppl;abs8500). Osimertinib may prolong DFS in adjuvant EGFRm-positive NSCLC. Methods: Trial Design ADAURA (NCT02511106) is a global, Phase III, double-blind, randomized study, assessing efficacy and safety of osimertinib vs placebo in patients with stage IBeIIIA non-squamous EGFRm-positive NSCLC with complete tumor resection. Approximately 700 patients from 210 sites will be randomized. A planned 60% of patients will be recruited from Asia, 40% from non-Asian countries; 70% stage IIeIIIA, 30% stage IB. Patients must be adults 18 years (Japan/Taiwan: 20) with primary NSCLC staged post-operatively as IB/II/IIIA, and central confirmation of Ex19del or L858R (alone or combined with other EGFR mutations including T790M). Complete surgical resection of the primary NSCLC is mandatory; patients will have baseline CT scans within 28 days prior to treatment confirming radiographic absence of residual disease. Complete surgical recovery is required for randomization; treatment to start at least 4 weeks following surgery. Patients who have received radiation therapy, preoperative chemotherapy, prior anticancer therapy or neoadjuvant/ adjuvant EGFR-TKI treatment are exempt. Standard post-operative adjuvant chemotherapy, consisting of a platinum-based doublet for 4 cycles maximum, is allowed; no more than 10 and 26 weeks may have elapsed between surgery and randomization for patients who have not or have received adjuvant chemotherapy, respectively. Patients will be randomized 1:1 to once-daily osimertinib 80 mg or placebo and stratified by stage (IB/II/IIIA), mutation type (Ex19Del/L858R) and race (Asian/non-Asian). Treatment may continue for 3 years in absence of discontinuation criteria including disease recurrence. Primary objective is to assess the efficacy of osimertinib vs placebo, measured by investigator-assessed DFS. Secondary objectives include assessment of the safety profile of osimertinib vs placebo; DFS rate at 2, 3, 5 years; overall survival (OS); 5-year OS rate; health-related quality of life; pharmacokinetics. Estimated primary completion date (final DFS data collection date): July 2021. Results: Not applicable. Conclusion: Not applicable.
PS03.01 Elective Nodal Irradiation for Limited-Stage Small Cell Lung Cancer: A survey of US Radiation Oncologists on Practices Topic: Radiation Oncology M.J. Farrell,1 J. Yahya,1 C. Degnin,1 Y. Chen,1 J.M. Holland,1 M.A. Henderson,1 J.J. Jaboin,1 M.M. Harkenrider,2 C.R. Thomas Jr.,1 T. Mitin1 1Radiation Medicine, Oregon Health and Science University, Portland, OR/US, 2Stritch School of Medicine, Loyola University Chicago, Chicago, IL/US Background: Elective nodal irradiation (ENI) has traditionally been used in clinical trials that have established thoracic radiotherapy (TRT) as instrumental in improving overall survival in patients with limitedstage small cell lung cancer (LS-SCLC). However, several publications suggest that omission of ENI may be appropriate. The current randomized trial CALGB 30610 mandates elective irradiation of ipsilateral hilar lymph nodes only, while EORTC 08072 (CONVERT) omitted ENI completely. Current US practice patterns are unknown in regards to ENI for patients with LS-SCLC. Methods: We surveyed practicing US radiation oncologists (ROs) via an IRB-approved online questionnaire. Questions covered background characteristics, self-rated knowledge of key trials, and treatment recommendations for LS-SCLC, based on several hypothetical clinical scenarios. Results: We received 309 responses from practicing ROs. Only a minority of respondents recommended ENI for patients with LS-SCLC: 21% for N0 disease, 29% for N1 disease, and 30% for N2 disease. 64% did not recommend ENI in any of these clinical scenarios. Respondents who recommended ENI were more likely to have been practicing over 10 years since residency training (p<0.01), more likely to be in private practice rather than an academic setting (p¼0.04), and less likely to be familiar with the ongoing CALGB 30610 trial (p¼0.04). Almost uniformly, respondents prescribe the same RT dose to the primary disease and involved lymph
Poster Sessions
S1575
nodes (93%). When delivering ENI, 36% prescribe the same dose to involved and elective nodes, whereas 64% prescribe a lower dose to elective nodes than involved nodes. Conclusion: In our survey of US ROs, 64% of respondents did not recommend ENI. This is a dramatic shift in practice, as a similar survey of ROs conducted in 2007 showed this number to be 18%. Physicians further away from residency training were more likely to recommend ENI. In the recent EORTC 08072 trial, which omitted ENI, overall survival was higher than previously reported and radiation toxicities were lower than expected in both treatment arms, lending further evidence that omitting ENI should be considered a standard treatment strategy at this time. Results from the CALGB 30610 trial with limited ENI will further elucidate the role of ENI. Education of patients and physicians is essential in aligning practice patterns with the best clinical evidence.
PS03.02 Amifostine as a Cytoprotectant in Small Cell Lung Cancer Topic: Radiation Oncology J. Pollock,1 A.E. Pollock2 1Radiation Oncology, The Schiffler Cancer Center, Wheeling, WV/US, 2Radiation Oncology, Schiffler Cancer Center, Wheeling, WV/US Background: Chemoradiotherapy-induced esophagitis remains a dose limiting toxicity experienced by 35% of patients with locally advanced lung cancer. Data has demonstrated a benefit to intravenous amifostine as a means of reducing acute esophagitis in patients receiving concurrent chemoradiotherpay in non-small cell lung cancer, though none have shown an effect in small cell lung cancer. Our center has adopted a subcutaneous injection schedule and we report our retrospective findings. Methods: 49 patients with stage 3 small cell lung cancer received concurrent thoracic chemoradiotherapy. Chemotherapy consisted of cisplatin (120 mg/m2) and etoposide (60 mg/m2) on days 1 and 21 along with conformal radiotherapy (RT) encompassing CT-identified gross tumor volume. Dose delivery was 150 cGy twice daily with a 6 hour inter-treatment interval (total dose 4500 cGy). In 32 patients (group 1), amifostine was delivered (500 mg, sc divided in two injections) prior to the second daily RT fraction on non-chemotherapy days. The remaining 17 patients (group 2) did not receive amifostine due to choice or intolerance of the drug. Results: Metrics of esophagitis included weight loss and opiate requirement. 31% of group 1 required opiates at a median RT dose of 3300 cGy. 42% of group 2 required opiates during treatment at a median dose of 2250 cGy. Other variables evaluated to determine an association between amifostine use and esophagitis included esophageal V20, V30, and V50. No significant relationship was identified. Figure 1 illustrates a later need for opiate use in the amifostine group but this did not reach significance. Conclusion: In this modern retrospective series of thoracic chemoradiotherapy for stage 3 small cell lung cancer, subcutaneous amifostine did not significantly reduce the incidence of esophagitis. Limitations include small sample size and, due to a trend in postponing the onset of esophagitis, our center continues this practice.
PS03.03 Salvage Therapy for Relapse after Stereotactic Body Radiation for Stage I Lung Cancer Topic: Radiation Oncology Z.A. Oaks, J. Bogart, T. Nsouli, P. Aridgides Radiation Oncology, SUNY Upstate, Syracuse, NY/US Background: To evaluate treatment outcomes of recurrent non-small cell lung cancer (NSCLC) following initial SBRT for stage I disease.
S1576 Methods: Retrospective review of patients treated with SBRT for stage I NSCLC from 2007-2017 who were found to have relapsed. Recurrences were classified as local (initial treated lesion), lobar (outside the treated lesion but confined to one lobe), nodal (hilum or mediastinum), or distant. Results: Out of 297 treated with SBRT, 61 patients were found to have recurrence including 5 local, 14 lobar, 18 nodal, and 24 distant. Local recurrences developed at a median 21.2 months (range 11.6-63.4) from SBRT, and salvage treatment included radiation with concurrent chemotherapy (2 patients), lobectomy (2 patients), or radiofrequency ablation (1 patient). Lobar recurrences developed in a median 12 months (1.3 to 44.2), and nodal recurrences developed with median 11.3 months (1.8 to 34.5). Of 7 patients treated definitively after lobar relapse, 6 patients developed subsequent distant or regional relapse. Four of 11 patients treated for nodal relapse were salvaged without subsequent relapse. Approximately 40% of patients with lobar or nodal relapse did not undergo salvage therapy often due to poor functional status. Treatment related grade 3 + toxicity was not reported for patients treated with definitive salvage therapy. Median overall survival was 51 months after local relapse, 16 months after lobar relapse, and 13.7 months after nodal relapse. Median survival was 46 months for patients receiving definitive salvage therapy for intrathoracic recurrence compared with 9.7 months for patients not treated definitively. Distant recurrences occurred with a median of 10.9 months (range 2.0-55.9) after SBRT, and median survival was only 6.2 months after distant relapse in this group. Conclusion: Salvage therapy is feasible in the majority of patients with local or locoregional relapse after SBRT for stage I NSCLC. The success of salvage therapy appears to correlate with site of relapse with an unexpected high rate of subsequent relapse in patients treated for lobar recurrence. Novel approaches should be considered for addressing systemic disease in this poor risk population of patients.
PS03.04 Stereotactic Body Radiation Therapy (SBRT) Experience in Lung Oligometastases Topic: Radiation Oncology P. Antonini, L. Larrea, E. López, V. González, J. Bea, C. Baños Radiation Oncology, Hospital Virgen del Consuelo, Valencia/ES Background: The aim of this study is to review our experience and evaluate the results of SBRT for lung oligometastases in terms of survival, local control and toxicity. Methods: The medical records of all patients treated at single institution between 2002 and 2016 were retrospectively analyzed. There were 102 patients with 136 lung metastases treated with SBRT. Primary tumors included: previously treated non-small cell lung carcinoma (52%), colo-rectal adenocarcinoma (36%), gastroesophageal tumors, melanoma, endometrial cancer, urologic (renal/vesical), thyroid neoplasms (2% each) and unknown primary (4%). All patients had Karnofsky Performance Status > 80% and systemic disease was controlled in 85%. Prior treatments included: chemotherapy (70%) and surgery to primary/metastases (58%). SBRT treatment was delivered with multiple static non-coplanar beams or arc therapy. Prescribed dose was either 45 Gy in 3 fractions or a single 30-Gy fraction, ensuring BEDs>100Gy. Dose constraints were set for spinal cord, lung and esophagus. Toxicity and radiologic response were assessed in follow-up visits, using RTOG-EORTC scores and radiologist reviewed reports (RECIST/OMS criteria). Survival rates and toxicities were estimated using Kaplan-Meier method. Results: Median age was 71 years (28-88), 40% were elderly (>75 years old). Median tumor volume was 5.2 cm3 (0.11-144). Median follow-up was 16 months (377). Overall survival is 89% and 66% at 1 and 2 years. Local control is 99,3%, the only local relapse occurred in neuroendocrine histology. Acute toxicities grade 2 or less occurred in 11 %: esofagitis, dermitis or chest pain. Asymptomatic radiographic neumonitis was detected in 7 %
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of patients. To date, no significant chronic toxicities have been recorded. Conclusion: Our experience includes a significant proportion of elderly patients with controlled systemic disease and good performance status. SBRT appears as an excellent option in lung metastases of various origins, given the encouraging results considering overall survival, local control and reported toxicity.
PS04.01 ADAURA: PhIII, Double-Blind, Randomized Study of Osimertinib vs Placebo in EGFR Mutation-Positive NSCLC Post-Tumor Resection Topic: Medical Oncology R.S. Herbst,1 Y. Wu,2 H. Mann,3 Y. Rukazenkov,3 M. Marotti,3 M. Tsuboi4 1Yale Cancer Center, Yale-New Haven Hospital, New Haven, CT/US, 2Guangdong Lung Cancer Institute, Guangdong General Hospital, Guangzhou/CN, 3AstraZeneca, Cambridge/GB, 4Division of Thoracic Surgery and Oncology, National Cancer Center Hospital East, Chiba/JP Background: EGFR-TKIs are standard first-line therapy in patients with EGFR sensitizing mutation (EGFRm)-positive advanced NSCLC. EGFR T790M resistance mutation is observed in >50% of patients with acquired resistance to EGFR-TKIs. Osimertinib is a third-generation, irreversible, CNS-active EGFR-TKI selective for EGFRm and T790M, recommended in patients with T790M-positive advanced NSCLC who have progressed on first-line EGFR-TKIs. In a recent study (NCT01405079), gefitinib treatment in patients with resected EGFRmpositive NSCLC significantly increased disease-free survival (DFS) vs vinorelbine+cisplatin: median 28.7 vs 18.0 months (hazard ratio 0.60 (95% CI 0.42e0.87), p¼0.005), warranting further investigation of EGFR-TKIs in this setting (Wu et al, J Clin Oncol 2017;35:suppl;abs8500). Osimertinib may prolong DFS in adjuvant EGFRm-positive NSCLC. Methods: Trial Design ADAURA (NCT02511106) is a global, Phase III, double-blind, randomized study, assessing efficacy and safety of osimertinib vs placebo in patients with stage IBeIIIA non-squamous EGFRm-positive NSCLC with complete tumor resection. Approximately 700 patients from 210 sites will be randomized. A planned 60% of patients will be recruited from Asia, 40% from non-Asian countries; 70% stage IIeIIIA, 30% stage IB. Patients must be adults 18 years (Japan/Taiwan: 20) with primary NSCLC staged post-operatively as IB/II/IIIA, and central confirmation of Ex19del or L858R (alone or combined with other EGFR mutations including T790M). Complete surgical resection of the primary NSCLC is mandatory; patients will have baseline CT scans within 28 days prior to treatment confirming radiographic absence of residual disease. Complete surgical recovery is required for randomization; treatment to start at least 4 weeks following surgery. Patients who have received radiation therapy, preoperative chemotherapy, prior anticancer therapy or neoadjuvant/ adjuvant EGFR-TKI treatment are exempt. Standard post-operative adjuvant chemotherapy, consisting of a platinum-based doublet for 4 cycles maximum, is allowed; no more than 10 and 26 weeks may have elapsed between surgery and randomization for patients who have not or have received adjuvant chemotherapy, respectively. Patients will be randomized 1:1 to once-daily osimertinib 80 mg or placebo and stratified by stage (IB/II/IIIA), mutation type (Ex19Del/L858R) and race (Asian/non-Asian). Treatment may continue for 3 years in absence of discontinuation criteria including disease recurrence. Primary objective is to assess the efficacy of osimertinib vs placebo, measured by investigator-assessed DFS. Secondary objectives include assessment of the safety profile of osimertinib vs placebo; DFS rate at 2, 3, 5 years; overall survival (OS); 5-year OS rate; health-related quality of life; pharmacokinetics. Estimated primary completion date (final DFS data collection date): July 2021. Results: Not applicable. Conclusion: Not applicable.