< PreviousCOSELA™ (trilaciclib) for injection, for intravenous use Initial U.S. Approval: 2021 BRIEF SUMMARY OF PRESCRIBING INFORMATION INDICATIONS AND USAGE COSELA is indicated to decrease the incidence of chemotherapy-induced myelosuppression in adult patients when administered prior to a platinum/etoposide-containing regimen or topotecan-containing regimen for extensive-stage small cell lung cancer (ES-SCLC). DOSAGE AND ADMINISTRATION Recommended Dosage The recommended dose of COSELA is 240 mg/m 2 per dose. Administer as a 30-minute intravenous infusion completed within 4 hours prior to the start of chemotherapy on each day chemotherapy is administered. The interval between doses of COSELA on sequential days should not be greater than 28 hours. Missed Treatment Session(s) If the COSELA dose is missed, discontinue chemotherapy on the day the COSELA dose was missed. Consider resuming both COSELA and chemotherapy on the next scheduled day for chemotherapy. Discontinuation of Treatment If COSELA is discontinued, wait 96 hours from the last dose of COSELA before resumption of chemotherapy only. Dose Modification for Adverse Reactions Withhold, discontinue, or alter the administration of COSELA to manage adverse reactions as described in Table 1 [see Warnings and Precautions (5)]. Table 1: Recommended Actions for Adverse Reactions Adverse Reaction Severity Grade*Recommended Action Injection site reactions including phlebitis and thrombophlebitis Grade 1: Tenderness with or without symptoms (e.g., warmth, erythema, itching) Interrupt or slow infusion of COSELA. If 0.9% Sodium Chloride Injection, USP is being used as a diluent/flush, consider changing to 5% Dextrose Injection, USP as appropriate for subsequent infusions. Grade 2: Pain; lipodystrophy; edema; phlebitis Interrupt infusion of COSELA. If pain not severe, follow instructions for Grade 1. Otherwise, stop infusion in extremity and rotate site of infusion to site in alternative extremity. If 0.9% Sodium Chloride Injection, USP is being used as a diluent/ flush, consider changing to 5% Dextrose Injection, USP as appropriate for subsequent infusions. Central access may also be considered. Grade 3: Ulceration or necrosis; severe tissue damage; operative intervention indicated. Grade 4: Life- threatening consequences; urgent interventions indicated. Stop infusion and permanently discontinue COSELA. Acute drug hypersensitivity reactions Grade 2: Moderate; minimal, local or noninvasive intervention indicated; limiting Activities of Daily Living (ADL). Stop infusion and hold COSELA until recovery to Grade ≤1 or baseline, then consider resuming COSELA. If Grade 2 recurs, permanently discontinue COSELA. Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. OR Grade 4: Life-threatening consequences; urgent intervention indicated. Permanently discontinue COSELA. Interstitial lung disease/ pneumonitis Grade 2 (symptomatic)Hold COSELA until recovery to Grade ≤1 or baseline, then consider resuming COSELA. If Grade 2 recurs, permanently discontinue COSELA. Grades 3: Severe symptoms; limiting self-care ADL; oxygen indicated. OR Grade 4: Life-threatening respiratory compromise; urgent intervention indicated (e.g., tracheotomy or intubation) Permanently discontinue COSELA. Other toxicities Grade 3: Severe or medically significant but not immediately life-threatening; hospitalization or prolongation of hospitalization indicated; disabling; limiting self-care ADL. Hold COSELA until recovery to Grade ≤1 or baseline, then consider resuming COSELA. If Grade 3 recurs, permanently discontinue COSELA. Grade 4: Life-threatening consequences; urgent intervention indicated. Permanently discontinue COSELA. * National Cancer Institute – Common Terminology for Adverse Events (NCI-CTCAE) Version 4.03x CONTRAINDICATIONS COSELA is contraindicated in patients with a history of serious hypersensitivity reactions to trilaciclib. Reactions have included anaphylaxis [see Warnings and Precautions (5.2)]. WARNINGS AND PRECAUTIONS Injection-Site Reactions, Including Phlebitis and Thrombophlebitis COSELA administration can cause injection-site reactions, including phlebitis and thrombophlebitis. Injection-site reactions, including phlebitis and thrombophlebitis, occurred in 56 (21%) of 272 patients receiving COSELA in clinical trials, including Grade 2 (10%) and Grade 3 (0.4%) adverse reactions (ARs). The median time to onset from start of COSELA was 15 days (range 1 to 542) and from the preceding dose of COSELA was 1 day (1 to 15). The median duration was 1 day (range 1 to 151 for the resolved cases). Injection-site reactions, including phlebitis and thrombophlebitis, resolved in 49 (88%) of the 56 patients and led to discontinuation of treatment in 3 (1%) of the 272 patients. Monitor patients for signs and symptoms of injection-site reactions, phlebitis, and thrombophlebitis, including infusion-site pain and erythema during infusion. For mild (Grade 1) to moderate (Grade 2) injection-site reactions, flush line/cannula with at least 20 mL of sterile 0.9% Sodium Chloride Injection, USP or 5% Dextrose Injection, USP after end of infusion. For severe (Grade 3) or life- threatening (Grade 4) injection-site reactions, stop infusion and permanently discontinue COSELA [see Dosage and Administration (2.2)]. Acute Drug Hypersensitivity Reaction COSELA administration can cause acute drug hypersensitivity reactions, including facial edema and urticaria. Acute drug hypersensitivity reactions occurred in 16 (6%) of 272 patients receiving COSELA in clinical trials, including Grade 2 reactions (2%). One patient experienced a Grade 2 anaphylactic reaction 4 days after receiving COSELA, which resolved with epinephrine, and treatment with COSELA was continued. The median time to onset from start of COSELA was 77 days (range 2 to 256) and from the preceding dose of COSELA was 1 day (range 1 to 28). The median duration was 6 days (range 1 to 69 for the resolved cases). Acute drug hypersensitivity reactions resolved in 12 (75%) of the 16 patients. Monitor patients for signs and symptoms of acute drug hypersensitivity reactions including facial, eye, and tongue edema, urticaria, pruritus, and anaphylactic reactions. For moderate (Grade 2) acute drug hypersensitivity reactions, stop infusion and hold COSELA until the adverse reaction recovers to Grade ≤1. For severe (Grade 3) or life-threatening (Grade 4) acute drug hypersensitivity reactions, stop infusion and permanently discontinue COSELA [see Dosage and Administration (2.2)]. Interstitial Lung Disease/Pneumonitis Severe, life-threatening, or fatal interstitial lung disease (ILD) and/or pneumonitis can occur in patients treated with cyclin-dependent kinases (CDK)4/6 inhibitors, the same drug class as COSELA. ILD/pneumonitis occurred in 1 (0.4%) of 272 patients receiving COSELA in clinical trials. The adverse reaction was Grade 3 and reported 2 months after discontinuing COSELA, in a patient receiving a confounding medication. The adverse reaction did not resolve. Monitor patients for pulmonary symptoms indicative of ILD/pneumonitis such as cough, dyspnea, and hypoxia. For recurrent moderate (Grade 2) ILD/pneumonitis, permanently discontinue COSELA. For severe (Grade 3) or life-threatening (Grade 4) ILD/pneumonitis, permanently discontinue COSELA [see Dosage and Administration (2.2)]. Embryo-Fetal Toxicity Based on its mechanism of action, COSELA can cause fetal harm when administered to a pregnant woman. Females of reproductive potential should use an effective method of contraception during treatment with COSELA and for at least 3 weeks after the final dose [see Use in Specific Populations (8.1, 8.3)]. ADVERSE REACTIONS The following clinically significant adverse reactions are described elsewhere in the label: • Injection-Site Reactions, including phlebitis and thrombophlebitis [see Warnings and Precautions (5.1)] • Acute Drug Hypersensitivity Reactions [see Warnings and Precautions (5.2)] • ILD/Pneumonitis [see Warnings and Precautions (5.3)] Clinical Trials Experience Because clinical trials are conducted under widely varying conditions, adverse reaction rates observed in the clinical trials of a drug cannot be directly compared with rates in the clinical trials of another drug and may not reflect the rates observed in clinical practice. The safety of COSELA was evaluated in Studies 1, 2, and 3 [see Clinical Studies (14)]. Patients received COSELA 240 mg/m 2 by 30-minute intravenous infusion prior to chemotherapy on each chemotherapy day. The data described in this section reflect exposure to COSELA among 240 patients (122 patients in the trilaciclib group and 118 patients in the placebo group) being treated for extensive stage-small cell lung cancer (ES-SCLC) in 3 randomized, double-blind, placebo-controlled trials: 32 patients with treatment naïve ES-SCLC received carboplatin (AUC 5 Day 1) + etoposide (100 mg/m 2 Days 1-3) every 21 days; 58 received carboplatin (AUC 5 Day 1) + etoposide (100 mg/m 2 Days 1-3) every 21 days + atezolizumab (1200 mg on Day 1) every 21 days; 32 patients with previously treated ES-SCLC received topotecan (1.5 mg/m 2 Days 1-5) every 21 days. Study 1: COSELA Prior to Etoposide, Carboplatin, and Atezolizumab (E/P/A) Patients with newly diagnosed ES-SCLC not previously treated with chemotherapy Study 1 (G1T28-05; NCT03041311) was an international, randomized (1:1), double-blind, placebo-controlled study of COSELA or placebo administered prior to treatment with etoposide, carboplatin, and atezolizumab (E/P/A) for patients with newly diagnosed ES-SCLC not previously treated with chemotherapy. The data presented below are for the 105 patients who received study treatment. Eighty-five percent of patients receiving COSELA and 91% receiving placebo completed 4 cycles of induction therapy. Study 2: COSELA Prior to Etoposide and Carboplatin (E/P) Patients with newly diagnosed ES-SCLC not previously treated with chemotherapy Study 2 (G1T28-02; NCT02499770) was an international, randomized (1:1), double-blind, placebo-controlled study of COSELA or placebo administered prior to treatment with etoposide and carboplatin (E/P) for patients with newly diagnosed ES-SCLC not previously treated with chemotherapy. The data presented below are for the 75 patients who received study treatment. Seventy-six percent of patients in the COSELA group and 87% of patients in the placebo group completed at least 4 cycles of therapy. The median duration of treatment was 6 cycles in each treatment group. Study 3: COSELA Prior to Topotecan Patients with ES-SCLC previously treated with chemotherapy Study 3 (G1T28-03; NCT02514447) was an international, randomized (2:1), double-blind, placebo-controlled study of COSELA or placebo administered prior to treatment with topotecan for patients with ES-SCLC previously treated with chemotherapy. The data presented below are for the 60 patients who received study treatment with the 1.5 mg/m 2 dose of topotecan. Thirty-eight percent of patients receiving COSELA and 29% of patients receiving placebo completed 5 or more cycles of therapy. The median duration of treatment was 3 cycles in each treatment group. Integrated Safety Analysis The adverse reaction summary presented in Table 3 are pooled safety results from Studies 1, 2, and 3. The patients included in the pooling are those randomized patients that received at least 1 dose of COSELA (122 patients) or placebo (118 patients). Seventy-one percent of patients receiving COSELA and 78% of patients receiving placebo completed at least 4 cycles of therapy. The median duration of treatment was the same (4 cycles) for patients receiving COSELA and placebo. Serious adverse reactions occurred in 30% of patients receiving COSELA. Serious adverse reactions reported in >3% of patients who received COSELA included respiratory failure, hemorrhage, and thrombosis. Permanent discontinuation due to an adverse reaction occurred in 9% of patients who received COSELA. Adverse reactions leading to permanent discontinuation of any study treatment for patients receiving COSELA included pneumonia (2%), asthenia (2%), injection-site reaction, thrombocytopenia, cerebrovascular accident, ischemic stroke, infusion-related reaction, respiratory failure, and myositis (<1% each). Fatal adverse reactions were observed in 5% of patients receiving COSELA. Fatal adverse reactions for patients receiving COSELA included pneumonia (2%), respiratory failure (2%), acute respiratory failure (<1%), hemoptysis (<1%), and cerebrovascular accident (<1%). Infusion interruptions due to an adverse reaction occurred in 4.1% of patients who received COSELA. The most common adverse reactions (≥10%) were fatigue, hypocalcemia, hypokalemia, hypophosphatemia, aspartate aminotransferase increased, headache, and pneumonia. The most frequently reported Grade ≥3 adverse reaction (≥5%) in patients receiving COSELA occurring at the same or higher incidence than in patients receiving placebo was hypophosphatemia. The most common adverse reactions reported in at least 5% of patients receiving COSELA with a ≥2% higher incidence compared to patients receiving placebo are shown in Table 3. Table 3: Adverse Reactions in ≥5% Patients with SCLC Receiving COSELA (with ≥2% Higher Incidence in COSELA Compared to Placebo) Adverse ReactionCOSELA (N=122)Placebo (N=118) All Grades a (%) Grade ≥3 (%) All Grades a (%) Grade ≥3 (%) Fatigue343272 Hypocalcemia b 24<121<1 Hypokalemia c 226183 Hypophosphatemia d 217162 Aspartate aminotransferase increased e 17<114<1 Headache13090 Pneumonia10787 Rash9<160 Infusion-related reaction8020 Edema peripheral704<1 Abdominal pain upper7030 Thrombosis7322 Hyperglycemia6230 a Graded per NCI CTCAE v4.03x b Hypocalcemia=calcium decreased (lab) or treatment-emergent adverse event (TEAE) preferred term ‘Hypocalcemia’ c Hypokalemia=potassium decreased (lab) or TEAE preferred terms ‘Hypokalemia,’ ‘Blood potassium decreased’ d Hypophosphatemia=phosphate decreased (lab) or TEAE preferred terms ‘Hypophosphatemia,’ ‘Blood phosphorus decreased’ e Aspartate aminotransferase increased=aspartate aminotransferase increased (lab) or TEAE preferred term ‘Blood aspartate aminotransferase increased’ Grade 3/4 hematological adverse reactions occurring in patients treated with COSELA and placebo included neutropenia (32% and 69%), febrile neutropenia (3% and 9%), anemia (16% and 34%), thrombocytopenia (18% and 33%), leukopenia (4% and 17%), and lymphopenia (<1% and <1%), respectively. DRUG INTERACTIONS Effect of COSELA on Other Drugs, Certain OCT2, MATE1, and MATE 2K Substrates COSELA is an inhibitor of OCT2, MATE1, and MATE-2K. Co-administration of COSELA may increase the concentration or net accumulation of OCT2, MATE1, and MATE-2K substrates in the kidney (e.g., dofetilide, dalfampridine, and cisplatin) [see Clinical Pharmacology (12.3)]. Refer to the prescribing information for these concomitant medications for assessing the benefit and risk of concomitant use of COSELA. Table 4: Potentially Significant Drug Interactions with COSELA DrugsRecommendationsComments Dofetilide The potential benefits of taking COSELA concurrently with dofetilide should be considered against the risk of QT interval prolongation. Increased dofetilide blood levels may occur in patients who are also receiving COSELA. Increased plasma concentrations of dofetilide may cause serious ventricular arrhythmias associated with QT interval prolongation, including torsade de pointes. DalfampridineThe potential benefits of taking COSELA concurrently with dalfampridine should be considered against the risk of seizures in these patients. Increased dalfampridine blood levels may occur in patients who are also receiving COSELA. Elevated levels of dalfampridine increase the risk of seizure. CisplatinClosely monitor for nephrotoxicity. Concurrent treatment with COSELA may increase the exposure and alter the net accumulation of cisplatin in the kidney, which may associate with dose-related nephrotoxicity. USE IN SPECIFIC POPULATIONS Pregnancy Risk Summary Based on the mechanism of action, COSELA can cause fetal harm when administered to a pregnant woman [see Clinical Pharmacology (12)]. There are no available human or animal data on COSELA use to evaluate for a drug-associated risk of major birth defects, miscarriage or adverse maternal or fetal outcomes. Advise pregnant women of the potential risk to a fetus. The background risk of major birth defects and miscarriage for the indicated population is unknown. All pregnancies have a background risk of birth defect, loss, or other adverse outcomes. However, the background risk of major birth defects is 2% to 4% and of miscarriage is 15% to 20% of clinically recognized pregnancies in the United States general population. Lactation Risk Summary There are no data on the presence of trilaciclib in either human or animal milk, the effects on the breastfed child or the effects on milk production. Because of the potential for serious adverse reactions in breastfed children, advise lactating women to not breastfeed while taking COSELA and for at least 3 weeks after the last dose. Females and Males of Reproductive Potential Pregnancy Testing Based on its mechanism of action, COSELA can cause fetal harm if administered to a pregnant woman [see Use in Specific Populations (8.1)]. Pregnancy testing is recommended for females of reproductive potential prior to initiating COSELA. Contraception COSELA can cause fetal harm when administered to pregnant women [see Use in Specific Populations (8.1)]. Advise female patients of reproductive potential to use effective contraception during treatment with COSELA and for at least 3 weeks after the final dose. Infertility No studies have been performed in humans to evaluate the effects of COSELA on fertility in either sex. Based on animal toxicology studies, COSELA may impair fertility in females of reproductive potential [see Nonclinical Toxicology (13.1)]. Pediatric Use Safety and effectiveness in pediatric patients have not been established. Geriatric Use In the pooled efficacy dataset from Studies 1, 2 and 3, 46% of 123 patients randomized to COSELA were ≥65 years of age, and 49% of 119 patients randomized to placebo were ≥65 years of age. No overall differences in safety or effectiveness of COSELA were observed between these patients and younger patients. Hepatic Impairment Use of COSELA is not recommended in patients with moderate or severe hepatic impairment. No dosage adjustment is recommended for patients with mild hepatic impairment (total bilirubin ≤ upper limit of normal [ULN] and aspartate aminotransferase [AST] > ULN, or total bilirubin >1.0 to 1.5 × ULN, irrespective of AST). The pharmacokinetics of COSELA have not been studied in patients with moderate or severe hepatic impairment (total bilirubin >1.5 × ULN, irrespective of AST) [see Clinical Pharmacology (12.3)]. PATIENT COUNSELING INFORMATION Injection Site Reactions, Including Phlebitis and Thrombophlebitis Inform patients of the signs and symptoms of injection-site reactions, including phlebitis and thrombophlebitis. Advise patients to contact their healthcare provider immediately for signs and symptoms of injection-site reactions, including phlebitis and thrombophlebitis [see Warnings and Precautions (5.1)]. Acute Drug Hypersensitivity Reactions Advise patients to contact their healthcare provider immediately for signs and symptoms of acute drug hypersensitivity reactions, including facial, eye, and tongue edema, urticaria, pruritis, and anaphylactic reactions [see Warnings and Precautions (5.2)]. Interstitial Lung Disease/Pneumonitis Advise patients to immediately report new or worsening respiratory symptoms [see Warnings and Precautions (5.3) and Dosage and Administration (2.2)]. Embryo-Fetal Toxicity Advise females of reproductive potential of the potential risk to a fetus and to inform their healthcare provider of a known or suspected pregnancy [see Use in Specific Populations (8.1)]. Advise females of reproductive potential to use effective contraception during treatment with COSELA and for at least 3 weeks after the final dose [see Use in Specific Populations (8.1, 8.3)]. Lactation Advise women not to breastfeed during treatment with COSELA and for at least 3 weeks after the final dose of COSELA [see Use in Specific Populations (8.2)]. Drug Interactions Advise patients to inform their health care providers of all concomitant medications, including prescription medicines, over-the-counter drugs, vitamins, and herbal products [see Drug Interactions (7)]. Distributed by: G1 Therapeutics, Inc. Durham, NC 27709 025991 10003 Rev. 2/2021 US-2100006 G1 Therapeutics™ and the G1 Therapeutics logo, COSELA™ and the COSELA logo are trademarks of G1 Therapeutics, Inc. ©2021 G1 Therapeutics, Inc. All rights reserved. US-2000067 02/2021TUESDAY, SEPTEMBER 14, 2021 | WORLDWIDE VIRTUAL EVENT11 RETREATMENT WITH SABR SHOWS SIMILAR SURVIVAL AS INITIAL SABR, BUT WITH WORSE LOCAL RECURRENCE RATES A retrospective, single- institution review shows that retreatment with stereotactic ablative radiotherapy (SABR) has similar progression-free (PFS) and overall survival (OS) as initial treatment with SABR. But retreatment has worse local recurrence rates and more acute grade 2 toxicities than initial treatment. “There were several attempts for applying SABR to previously irradiated lung regions, with a wide range of local control and toxicity rates reported, possibly due to heterogeneous clinical settings,” said Tae Hoon Lee, MD, Department of Radiation Oncology at South National University Hospital, Republic of Korea, during OA11: Early Stage NSCLC. “Safety and efficacy of re- irradiation with SABR needed to be evaluated.” Researchers identified 337 patients who received lung SABR for primary, recurrent, or metastatic lung cancer between 2013 and 2018. Of this group, 21 patients had re- treatment with SABR. Using propensity score matching for age, tumor histology, underlying pulmonary disease, tumor size, and tumor locations, the group built a 1:3 matched cohort of 63 patients who had received initial SABR. Treatment was based on 4D cone-beam computed tomography (4D-CBCT) with the internal target volume (ITV) set for the complete lung tumor and the planning target volume (PTV) as ITV plus 3-7 millimeters. The prescribed radiation dose was at the discretion of the treating clinician. Clinical outcomes measured included local control, distant metastasis-free survival (DMFS), PFS, and OS. There were no significant differences between the treatment group and matched controls, Dr. Lee reported. Just over one-half (57.1%) were 75 years of age or younger, 81% were male, 38.1% had underlying pulmonary disease, and 71.4% had a history of smoking. Median time to re-irradiation was 13.7 months, and there was no significant difference between doses across the two groups. The local control rate for initial SABR was 93.2% at 1 year, 88.3% at 2 years, and 88.3% at 3 years. Local control rates for retreatment were 75.2%, 65.2%, and 65.2% respectively (P = 0.019). There were no significant differences in DMFS, PFS, or OS between the two groups. There were no overall differences in grade 2 or higher cough, dyspnea, or chest wall pain between the two groups, but the retreatment group had a significantly higher rage of acute toxicity, 28.6% vs. 6.3%. “It is interesting to note that the median treatment volume for this second treatment was on the small side, with a median ITV volume of almost six millimeters and a median PTV of twenty-one millimeters,” noted discussant Pamela Samson, MD, MPHS, associate professor of radiation oncology at Washington University and Siteman Cancer Center in St. Louis. “I hope to learn more about how patients are selected for repeat SABR, as not all patients may be good candidates for this approach.” ADDITION OF PD-L1 INHIBITOR TO NEOADJUVANT THERAPY, MAINTENANCE, SAFE FOR RESECTABLE MPM RESULTS FROM A FEASIBILITY trial in patients with resectable malignant pleural mesothelioma (MPM) indicated that neoadjuvant cisplatin-pemetrexed-atezolizumab followed by resection and maintenance atezolizumab met safety criteria, with more than one-half of patients proceeding to maintenance therapy. Anne Tsao, MD, University of Texas MD Anderson Cancer Center, presented the results during OA13: Topics of Pleural Mesothelioma. MPM is an orphan disease with limited treatment options. In the curable population, neoadjuvant chemotherapy, surgical resection, and adjuvant radiation yield a median overall survival (OS) of 17 to 25 months, Dr. Tsao said. MPM is an immunogenic disease, and PD-L1 is often associated as a negative prognostic marker. “We proposed that adding an anti–PD-L1 inhibitor to neoadjuvant cisplatin-pemetrexed and then maintenance immunotherapy after surgical resection and, potentially, adjuvant radiation will enhance T-cell activation against microscopic disease and potentially increase overall survival outcomes,” Dr. Tsao said. Included patients were enrolled from November 2017 to May 2020 and had epithelioid or biphasic histology. Safety was defined as no grade 4/5 immune-related adverse event, and feasibility was at least 75% of patients having received at least one dose of maintenance therapy. Patients were enrolled into two cohorts by resection— pleurectomy/decortication (P/D; 24 planned) or extrapleural pneumonectomy (EPP; four planned)—and received four cycles of neoadjuvant cisplatin- pemetrexed-atezolizumab. If there was no disease progression, they went on to resection, radiation for EPP cases, and 1 year of maintenance atezolizumab. Twenty-eight patients were eligible; 25 received at least two cycles of cisplatin-pemetrexed- atezolizumab. Eighteen patients underwent surgical resection, and 15 received maintenance atezolizumab. One patient remains ongoing with maintenance atezolizumab therapy. For the neoadjuvant therapy, the treatment-related adverse events included one grade 4 acute renal injury, pneumonitis, sepsis, and respiratory failure. Most adverse events were predominantly grade 1 or 2. For maintenance atezolizumab the most common treatment- related adverse events were also predominantly grade 1 or 2. There were no grade 4/5 adverse events. Preliminary survival results at an early median follow-up of 10.3 months were presented. The median OS was not yet reached. Median progression-free (PFS) survival was 18.6 months. “This trial highlights the challenging nature of neoadjuvant therapy trials in this patient population,” Dr. Tsao said. “We need to conduct more research with window-of-opportunity studies to identify biomarkers predictive of benefit to these different treatments we give our patients.” Harvey I. Pass, MD, of NYU Langone Health, discussed the presented data and several questions that remain, including how were responses measured, what was the influence of histology on responses or early endpoints, and what was the influence of PD-L1 expression on pre-treatment biopsy? “Neoadjuvant immunochemo- [therapy] and neoadjuvant double checkpoint inhibition trials will help answer which protocols are safest with the longest PFS and OS, as well as answer translational ques- tions,” Dr. Pass concluded. Anne Tsao, MD Tae Hoon Lee, MD12IASLC WORLD CONFERENCE ON LUNG CANCER | #WCLC21 #LALCA21 www. IASLC.org/lalca-2021 The 2021 LALCA Schools of Thoracic Oncology Meeting will host several unique, intense workshops from different disciplines including thoracic oncology, advocacy, nursing, and pathology, specifically designed for young researchers in Latin America. CONQUERING THORACIC CANCERS WORLDWIDE VIRTUAL MEETING Save the Date! 2021 LALCA Schools of Thoracic Oncology DECEMBER 3-4, 2021 | WORLDWIDE VIRTUAL EVENT REGISTRATION OPENING SOON! SOCIAL VULNERABILITY A RISK FACTOR IN LUNG CANCER SURGICAL OUTCOMES SOCIOECONOMIC STATUS HAS LONG BEEN associated with access to health care and outcomes of treatment. A new analysis of patients with early-stage lung cancer in Brazil found that social vulnerability is an independent risk factor for patients undergoing surgical treatment. “Emerging countries like Brazil have very high levels of social inequality and lung cancer is one of the most common tumors in Brazil,” said Ricardo Terra, MD, professor of thoracic surgery at the University of São Paulo, Brazil. “Understanding the role of social vulnerability in this disease is essential for the development of specific public policies to better implement clinical trial resources and to better understand how to treat patients.” Researchers identified 881 patients with stage I disease, 523 of whom who received surgical treatment in São Paulo hospitals from January 2000 through December 2013. Patients were stratified by the São Paulo Vulnerability Index (IPVS), a six-point scale of social vulnerability from extremely low vulnerability (1) to very high vulnerability (6). Scores are based on each patient’s place of residence and location-based factors such as mean income, education level, access to healthcare, and local infrastructure investment such as the condition of roads. Dr. Terra discussed the results of the study during OA14: Global Disparities in Lung Cancer Care on Sunday. Just over one- half of patients, 53.2%, were male and their average age was 64. Just under one-half of patients, 49.6, had an IPVS of 2, very low vulnerability. The average time from diagnosis to treatment was 28.4 days, and 54% had adenocarcinoma. Median survival was 87 months, and 5-year survival was approximately 52%, Dr. Terra reported. IPVS emerged as the most important independent variable for 30-day mortality, with an odds ratio (OR) of 1.73 for high IPVS scores (P = 0.001). Older patients had slightly worse 30-day outcomes (OR = 1.06; P = 0.012). Neither histologic type nor gender were statistically significant. “Social vulnerability has a strong impact in the surgical survival of patients with stage I disease,” he said. Multivariate analysis showed similar results. High IPVS was the most important risk factor for early mortality (HR = 1.28; P < 0.001), followed by age (HR = 1.03; P < 0.001). Histologic type was not a risk factor for these early-stage patients, and female gender was protective (HR = 0.62; P < 0.001). “This study confirms that social vulnerability is an independent risk factor in the studied population, which is also reported in previous studies,” said discussant Nan Wu, MD, professor of thoracic surgery at Peking University Cancer Hospital, China. “More and more evidence indicate that social vulnerability may directly influence the surgical outcome. Decreasing social vulnerability and providing equal opportunity for the general population are urgent needs.” Ricardo Terra, MD Results Overall survival: median of 87 months (32-0) Figure 1. Kaplan-Maier survival curve (n=495) number at risk Probability of survival 050100150200 49524780183 meses 0.00 0.25 0 .50 0 .75 1 .00INNOVATIONS IN LUNG CANCER DETECTION and Management of Non-Small Cell Lung Cancer (NSCLC) With Targeted Therapy INDUSTRY–SPONSORED SYMPOSIUM AT IASLC 2021 WORLD CONFERENCE ON LUNG CANCER FRIDAY, SEPTEMBER 10, 2021 | 5:45 AM – 6:45 AM MT Joshua Sabari, MD Assistant Professor Department of Medicine, Medical Oncology New York University School of Medicine New York, NY Ticiana Leal, MD Associate Professor Hematology/Oncology University of Wisconsin School of Medicine and Public Health Madison, WI Christopher J. Manley, MD Director, Interventional Pulmonology Fox Chase Cancer Center Philadelphia, PA DISCLAIMER: This educational event is sponsored by Janssen Pharmaceuticals, Inc., and is not eligible for CME credit. The speakers are paid consultants of Janssen Pharmaceuticals, Inc. This program was approved by the IASLC 2021 World Conference on Lung Cancer Program Committee as an independent activity held in conjunction with the IASLC 2021 World Conference on Lung Cancer. This program is not sponsored or endorsed by IASLC and is not part of the official IASLC accredited program. FACULTY OVERVIEW AND LEARNING OBJECTIVES Lung cancer is commonly diagnosed at advanced or late stages. Although lung cancer is the major cause of cancer mortality, there are still substantial challenges with screening, early detection, and prompt intervention. Despite development of therapies aimed at treating lung cancers driven by specific genetic mutations such EGFR, KRAS, MET, BRAF, and ALK, detection and recognition of specific driver mutations, adequate tissue sampling for initial diagnosis and potential follow-up testing, and development of resistance to current targeted treatments remain key challenges for improving survival and other clinically important outcomes. By the end of this symposium, participants should be able to: •Describe current advances for the diagnosis and management of advanced stage NSCLC with EGFR mutations (common and ex20ins) •Discuss recent progress in detection and early intervention in patients with lung cancer • Identify actions for addressing current unmet needs and discuss future directions AGENDA Welcome and Introduction Joshua Sabari, MD EGFR-mutated NSCLC – Progress, Recent Developments, and Unmet Needs Ticiana Leal, MD Advances in Early Diagnosis, Detection, and Intervention of Lung Cancer Christopher J. Manley, MD Q&A All panelists14IASLC WORLD CONFERENCE ON LUNG CANCER | #WCLC21 NADIM, CONTINUED FROM THE COVER … JTO Impact Factor increases to 15.609 The Highest Yet JOURNAL OF THORACIC ONCOLOGY The Journal of Thoracic Oncology (JTO), the IASLC’s official journal, is the field’s authoritative publication for education and information related to all aspects of thoracic malignancies. The JTO includes original research, reviews, and opinion pieces, and reaches a diverse audience. The JTO’s influence on the field is represented by its increased impact factor, which has climbed dramatically in recent years. From having an impact factor of 6.595 in 2016, the JTO’s impact rose to 13.357 in 2019 and to 15.609 in 2020. Additionally, it ranks 13th out of all oncology journals and 4th out of all respiratory system publications. jto.org | jtocrr.org with Dr. Stephen Liu and Dr. Narjust Duma The official podcast of the IASLC. Tune in each month for conversations with the researchers, healthcare professionals, patients and advocates from around the world who are making a difference in the treatment of thoracic cancers. Find new podcast episodes at IASLC.org/Lung-Cancer-Considered. Lung Cancer Considered is funded in part by Amgen, AstraZeneca, Lilly Oncology, and Merck KGaA Darmstadt Germany. of patients with stage IIIA NSCLC were published in 2020. At diagnosis, more than one-third of patients with NSCLC have stage III disease, Dr. Provencio noted. Neither surgical resection nor radiotherapy alone are associated with good outcomes. Micrometastatic disease is often present when the N2 nodes are involved. Most patients eventually relapse, and two-thirds of the relapses are systemic. The combination of chemotherapy and immunotherapy (CT-IO) has a high response rate and longer survival in unselected patients with NSCLC, he continued, but NADIM is among the first trials of this combination in the neoadjuvant setting. TRIAL DETAILS A total of 46 patients were enrolled in the single-arm, open-label study between April 26, 2017, and Aug. 25, 2018, at 18 hospitals in Spain. Patients were 18 years or older with histologically or cytologically documented treatment-naïve stage IIIA N2 or T4NO/N1 NSCLC. All patients were judged to be good surgical candidates by a local multidisciplinary clinical team and had an Eastern Cooperative Oncology Group (ECOG) performance status of 0 or 1. Patients received intravenous neoadjuvant nivolumab (360 mg) plus paclitaxel (200 mg/m 2 ) plus carboplatin (area under curve 6; 6 mg/mL per minute) on Day 1 of three 21-day cycles. Patients who showed no sign of progression continued onto surgery during the third or fourth week of the third neoadjuvant cycle. After surgery, patients received 480 mg of intravenous nivolumab monotherapy every 4 weeks for 8 months. The primary endpoint was 24-month progression-free survival (PFS) in a modified ITT population which included all patients who received neoadjuvant treatment, and in the per-protocol (PP) population, which included all patients who underwent resection and received at least one adjuvant dose of nivolumab. Planned secondary endpoints included 3-year OS and an exploratory analysis of ctDNA as a prognostic biomarker. The initial PFS, reported in 2020, was 77.1%. Dr. Provencio presented 3-year follow up results as well as continuing safety data and results this year. Median follow up was 38 months, he noted, with 94% of patients having reached the planned 36-month follow up mark. Follow up is ongoing. In all, 41 patients underwent tumor resection, and 37 patients received adjuvant therapy. Most patients, 58.7%, received complete adjuvant therapy of 16-17 cycles, and 21.7% received between three and 15 cycles. There was no interruption of nivolumab administration during the planned 17-cycle adjuvant course. Within the cohort, 12 patients (26.1%) progressed, and nine patients (19.6%) of the ITT population died. Three deaths were patients who had disease progression following neoadjuvant treatment and did not undergo surgery, four patients who underwent surgery later died, and two patients were disease-free after surgery but died from COVID-19. In the ITT population, PFS was 69.6% at 36 months and at 42 months and 81.1% in the PP population. Median PFS for patients with progressive disease was 21.4 months. OS in the ITT population was 81.9% at 36 months and 78.9% at 42 months. OS in the PP population was 91.0% at 36 months and 87.3% at 42 months. Clearance of ctDNA following neoadjuvant therapy emerged as a reliable prognostic marker for survival in this small population, with a hazard ratio of 0.05 (p = 0.024). The most common toxicities seen TUESDAY, SEPTEMBER 14, 2021 | WORLDWIDE VIRTUAL EVENT15 RecordTimeResults.com › RESULTS REVEALED IN RECORD TIME BECAUSE TIME MATTERS advanced cancerpatients in 3-5 business days* Low QNS † rate means more patients get tested and treated Minimal tissue requirements: As small as a grain of rice Personalized guideline- and clinical trial-driven treatment recommendations *Data on file. Turnaround time is based on qualified sample receipt. Comparative turnaround time data on file. Oncotype MAP Pan-Cancer Tissue is a trademark of Genomic Health, Inc. Exact Sciences is a registered trademark of Exact Sciences Corporation. © 2021 Genomic Health, Inc. All rights reserved. Scan to explore test benefits SCREENING, CONTINUED FROM THE COVER … random assignment, Dr. Field noted. Of the 161 participants diagnosed with lung cancer, 100 died from any cause. The number of deaths among participants in the screening arm was significantly lower than in the control arm (42 vs. 58; RR = 0.52; 95% CI: 0.35-0.77; P = 0.001). This difference was also significant for men (RR = 0.52; 95% CI: 0.32-0.82; P = 0.005), but not women. There were also significantly fewer late- stage lung cancers in the screening arm compared with the control arm (P = 0.005). Because the UKLS pilot study was not powered for a reduction in lung cancer mortality, the researchers also conducted the meta-analysis, which included randomized trials published up to November 2, 2020 with at least 3 years median follow-up. In addition to the reduction in lung cancer mortality, results from the meta-analysis showed a small reduction in all-cause mortality (RR = 0.97; 95% CI: 0.94-1.00). Dr. Field noted that even this small reduction represents a large number of lives saved. In a discussion of these results, Annette McWilliams, MBBS, FRACP, MD, FRCPSC, Fiona Stanley Hospital, University of Western Australia, said this meta-analysis is like two other meta-analyses recently published that did not include the UKLS trial data. All three meta-analyses had similar results, she said. However, Dr. McWilliams did highlight a few important things about the results presented by Dr. Field. First, she said, the vast majority of participants in all screening trials are men; only 30% are women. “This highlights the inequity of enrollment of female participants in looking at the impact of screening in women in our work so far,” Dr. McWilliams said. In addition, the UKLS is the only study that used a risk prediction model for enrollment. The UKLS also noted a significant reduction in all-cause mortality that was much greater than that seen in other studies. “Mortality benefit of LDCT screening is now widely accepted,” Dr. McWilliams said. “Design of screening programs will need ongoing adjustment and fine-tuning to perform better for different cohorts.” during neoadjuvant treatment were linked with chemotherapy, including neutropenia. There were few grade 3-4 treatment-related adverse events and no treatment-related fatalities. One patient withdrew from the study and received only two neoadjuvant cycles. “NADIM shows that the OS more than doubles with the addition of nivolumab before and after surgery compared to historical studies,” said discussant Bruna Pellini, MD, assistant member of the H. Lee Moffitt Cancer Center and assistant professor of thoracic oncology at the University of South Florida Morsani College of Medicine. “The question is whether these results will translate to larger populations, and I believe they will, though perhaps the effect size won’t be as large as displayed here.” Another important finding is the potential use of ctDNA as a predictor of response. One element not seen was a subanalysis of patients with N2 disease. “We should study that because patients with N2 disease have a higher risk of local relapse,” Dr. Pellini said. “I would like to see their outcomes compared to patients who did not have N2 disease.” NADIM, CONTINUED FROM OPPOSITE PAGE … 2021 HOT TOPIC MEETING: SMALL CELL LUNG CANCER OCTOBER 29-30, 2021 | WORLDWIDE VIRTUAL EVENT CONQUERING THORACIC CANCERS WORLDWIDE #SCLC21 www.IASLC.org/SCLC-2021 VIRTUAL MEETING REGISTER NOW! This meeting will focus on preclinical and clinical advances in small cell lung cancer (SCLC) research, including, but not limited to, basic research on oncogenesis and biology of disease, preclinical therapeutic research, and highlights of ongoing clinical translation. The #SCLC21 aims to provide a “state-of-the-state” update on recent progress in small cell lung cancer research, to establish a forward-looking perspective on key unanswered questions in the field, and to promote research collaboration among small cell lung cancer investigators. Sponsorship Opportunities Available! 2021 HOT TOPIC MEETING: SMALL CELL LUNG CANCER OCTOBER 29-30, 2021 | WORLDWIDE VIRTUAL EVENT CONQUERING THORACIC CANCERS WORLDWIDE #SCLC21 www.IASLC.org/SCLC-2021 VIRTUAL MEETING REGISTER NOW! This meeting will focus on preclinical and clinical advances in small cell lung cancer (SCLC) research, including, but not limited to, basic research on oncogenesis and biology of disease, preclinical therapeutic research, and highlights of ongoing clinical translation. The #SCLC21 aims to provide a “state-of-the-state” update on recent progress in small cell lung cancer research, to establish a forward-looking perspective on key unanswered questions in the field, and to promote research collaboration among small cell lung cancer investigators. Sponsorship Opportunities Available! PRECISION ONCOLOGY: THE CLINICAL ROLE OF TRK FUSIONS AS THE PRIMARY ONCOGENIC DRIVER IN TRK FUSION CANCER Dr Luis Raez, Chief Scientific Officer, Memorial Cancer Institute Please join this program to learn about: • clinical efficacy and safety of a TRK inhibitor • a testing method to identify appropriate patients for treatment with a TRK inhibitor • strategic approaches to using a TRK inhibitor through case illustrations On demand from September 20–December 17 © 2021 Bayer. BAYER and the Bayer Cross are registered trademarks of Bayer. PP-PF-ONC-US-2039-1 08/21 TRK, tropomyosin receptor kinase. Program for Lung Specialists LEARN MORENext >