Kristi Rosa

A retrospective study has suggested that immunotherapy may have a great survival benefit in the frontline setting for patients with metastatic non–clear cell renal cell carcinoma (RCC) than select targeted therapies. 

Results of the analysis presented during the 2021 Genitourinary Cancer Symposium showed that among 1181 patients with metastatic RCC, the median overall survival (OS) in those who received an immune checkpoint inhibitor–based regimen was 28.6 months (95% CI, 17.4–not reached) versus 19.2 months (95% CI, 16.7-21.9) with a VEGF inhibitor and 12.6 months (95% CI, 10.3-14.5) with an mTOR inhibitor.

Moreover, the median time-to-treatment failure (TTF) in those who received an immunotherapy-based regimen was also longer at 6.9 months (95% CI, 2.8-14.0) versus 5.1 months with a VEGF inhibitor (95% CI, 4.6-5.7) and 3.9 months (95% CI, 3.0-5.1) with an mTOR inhibitor.

In the entire population of patients included in the analysis, the objective response rate (ORR) achieved in those who received an immunotherapy-based regimen was 25%; it was 17.8% in those who received VEGF targeted therapy and 5.8% in those who received mTOR-targeted treatment (

“Immune checkpoint inhibitor–based frontline therapy appears to be associated with improved OS compared to VEGF and mTOR targeted therapy in treatment-naïve metastatic non–clear cell RCC, even after adjustment for International Metastatic RCC Database Consortium [IMDC] risk, histology, and age,” lead study author Jeffrey Graham, MD, of the University of Manitoba, and colleagues, wrote in a poster on the data.

Immunotherapy options have induced impressive activity in patients with metastatic clear-cell RCC; as such, these options have become part of standard frontline treatment. Although non–clear cell RCC represents about 15% of all kidney cancers, findings supporting the efficacy of immune checkpoint inhibitors up front has remained largely limited.

To address this need, investigators launched a study to detail the real-world effectiveness of frontline approaches containing immune checkpoint inhibitors in patients with metastatic non–clear cell RCC.

To perform a retrospective analysis of the IMDC, investigators included all patients who had non–clear cell histology. Patients were categorized into 3 groups based on first-line treatment: single-agent VEGF therapy, single-agent or combination immunotherapy, and single-agent mTOR therapy. For the analysis, investigators looked at outcomes, such as ORR, TTF, and OS.

The median age of the entire patient population was 60.6 years, 65.4% were male, 76.4% had undergone nephrectomy, and 16.6% had sarcomatoid features. The most common histologic subtype across the groups was papillary disease (54.2%), and most patients fell into the intermediate IMDC risk group (55.1%). Across the groups, 25.1% of patients had liver metastases, 34.2% had bone metastases, and 3.6% had brain metastases.

Of the 1181 patients included in the analysis, 78.2% had received VEGF treatment (n = 924), which included sunitinib (Sutent; n = 632; 68.4%), pazopanib (Votrient; n = 171; 18.5%), sorafenib (Nexavar; n = 72; 7.8%), cabozantinib (Cabometyx; n = 12; 1.3%), or other (n = 37; 4%). Moreover, 15.8% had received mTOR inhibitors (n = 186) in the frontline setting, such as temsirolimus (Torisel; n = 141; 75.8%) or everolimus (Afinitor; n = 45; 24.2%).

The remaining 5.5% had received immune checkpoint inhibitor–based therapy (n = 65), which could include nivolumab (Opdivo) and ipilimumab (Yervoy; n = 20; 30.8%), atezolizumab (Tecentriq) plus bevacizumab (Avastin; n = 14; 21.5%), nivolumab (n = 13; 20.0%), pembrolizumab (Keytruda; n = 13; 20.0%), or other (n = 5; 7.7%).

Investigators performed a multivariable Cox regression analysis to adjust for imbalances in prespecified prognostic covariates, such as IMDC risk, histologic subtype, and age. Results revealed that the hazard ratio (HR) for OS between immune checkpoint inhibitor–based therapy and VEGF treatment was 0.58 (95% CI, 0.35-0.94; 

= .03), while it was 0.48 (95% CI, 0.29-0.80; 

= .005) for immunotherapy-based treatment versus mTOR therapy.

Additionally, the HR for TTF with immunotherapy-based treatment versus VEGF therapy was 0.72 (95% CI, 0.72; 95% CI, 0.51-1.0; 

= .06) and it was 0.54 (95% CI, 0.37-0.78; 

= .001) for immunotherapy-based treatment versus mTOR treatment.

When looking at ORR per histologic subgroup, those with papillary disease who received VEGF treatment experienced an ORR of 13.0% versus 3.7% with mTOR therapy and 31.6% with immunotherapy-based treatment (

= .002). In patients with the chromophobe subtype, the ORRs were 20.6% versus 13.6% versus 9.1% in those who received VEGF therapy, mTOR therapy, and an immunotherapy-based regimen, respectively (

= .527). Those with an unclassified disease subtype experienced ORRs of 15.2%, 0%, and 33.3%, respectively (

“The ORR of 25% in the entire population is consistent with the existing literature of immune checkpoint inhibitor therapy in non–clear cell RCC, with lower responses seen in the chromophobe subgroup and higher responses seen in the papillary subgroup,” the authors of the poster wrote. “The study population was predominantly papillary RCC, and the effectiveness of immune checkpoint inhibitor–based therapy in other less common histologic subtypes remains inconclusive.”

The results yielded from the analysis must be confirmed in prospective, randomized clinical trials, the authors concluded.

Graham J, Wells C, Dudani S, et al. Effectiveness of first-line immune checkpoint inhibitors (ICI) in advanced non-clear cell renal cell carcinoma. 

. 2021;39(suppl 6):316. doi:10.1200/JCO.2021.39.6_suppl.316

Articles

A retrospective study has suggested that immunotherapy may have a great survival benefit in the frontline setting for patients with metastatic non–clear cell renal cell carcinoma (RCC) than select targeted therapies.

OS Benefit Suggested for Frontline IO Versus TKIs in Metastatic Non–Clear Cell RCC

Results from 2 phase 3 clinical trials showed that use of the investigational gene cell therapy betibeglogene autotemcel (beti-cel) led to durable transfusion independence in 87% of pediatric patients under the age of 18 years with transfusion-dependent beta-thalassemia (TDT) with a median average hemoglobin (Hb) of 11.3 g/dL, according to a presentation given as part of the 2021 Transplantation and Cellular Therapy Meetings.

The transfusion independence was maintained by having a dominant HbA787Q fraction in the blood, lead study author Mark C. Walters, MD, who is also the program director of Blood & Marrow Transplantation, program director of the Cord Blood Program, and medical director of the Jordan Family Center for BMT & Cellular Therapies Research, said during an oral presentation delivered on the data.

Moreover, the median weighted average Hb during transfusion independence was 10.1 g/dL in patients under the age of 12 years (n = 4) and 11.4 g/dL in patients between 12 years of age and 18 years (n = 9).

“Overall, the transfusion independence rate was very similar to the adults examined in the phase studies, which had been 83%,” said Walters. “Ineffective erythropoiesis was improved but not eliminated after beti-cel, and the treatment regimen with the gene therapy in pediatric patients less than 18 years of age had a tolerability profile that was consistent with the known effects of myeloablation with single-agent busulfan.”

Beti-cel was developed with the goal of establishing lifelong, functional adult Hb that permits transfusion independence without the need for a donor. To manufacture the product, stem cells are collected from the patient’s blood and then they are altered by a virus that brings working copies of the beta-globin gene into the cells.

 When the cells are returned to the patient, they are delivered via the bloodstream to the bone marrow; once there, they create healthy red blood cells that, in turn, produce beta-globin.

Currently, the gene therapy is under investigation in two phase 3 trials: HGB-207 (Northstar-2) and HGB-212 (Northstar-3). To be eligible for enrollment, patients had to be 50 years of age or younger and have TDT. Specifically, for HGB-207, patients had to have a non

“These are individuals who have some endogenous Hb production, but not enough to avoid regular transfusions,” noted Walters. HGB-212 enrolled patients with the β0/β0 genotype, which is “more severe, and is characterized by having very little or no endogenous Hb production,” added Walters.

Once the safety and efficacy of the gene therapy was established, investigators expanded the research to include pediatric participation. To this end, 26 patients under the age of 18 years were enrolled to the phase 3 trials; they were broken into 2 subgroups: those less than 12 years of age (n = 14; 8 on HGB-207 and 6 on HGB-212) and those between 12 years and 18 years (n = 12; 6 on HGB-207 and 6 on HGB-212).

These patients proceeded to mobilization with granulocyte colony stimulating factor and plerixafor followed by apheresis. As part of the centralized manufacturing process, CD34-positive cells were selected, hematopoietic stem cells were transduced with BB305 lentiviral vector, and then the cells were cryopreserved.

Once shipped back to the transplant center, patients undergo myeloablative conditioning with single-agent busulfan and then the 24 patients were then infused with the gene therapy; 13 patients younger than 12 years received beti-cel (8 on HGB-207 and 5 on HGB-212), while 11 patients between 12 years and 18 years received the product (6 on HGB-207 and 5 on HGB-212).

The median follow-up following infusion was 15.5 months (range, 1.1-29.5). Patients were monitored for hematological recovery, including recovery in erythroid cells that have HbA787Q, the gene therapy Hb, according to Walters. “There’s a single amino acid substitution that permits this Hb to be measured directly after the drug product has been infused, and also the duration can be established,” noted Walters.

The follow-up for this study is 2 years, although patients are provided with the option to participate in long-term follow-up that will continue through 13 years.

At baseline, 46% of those in the cohort of patients less than 12 years (pediatric cohort) were male, as well as 64% of those in the cohort of patients between 12 years and 18 years (adolescent cohort). The median age at assent in the 2 cohorts was 8 years and 15 years, respectively. “Most of the patients had mild to moderate liver iron loading, but there was no cardiac iron loading,” noted Walters.

β0/β0 genotype in the pediatric cohort versus 64% of those in the adolescent cohort; 23% and 36% of patients, respectively, had the β0/β0 genotype. Only 1 patient had a splenectomy prior to trial enrollment and the majority of participants commenced red cell transfusions within their first year of life, added Walters.

The majority of patients had sufficient stem cells mobilized and collected after only 1 mobilization cycle (86%, pediatric; 83%, adolescent), while a smaller fraction required 2 cycles to collect enough cells for product manufacturing (14% and 17%, respectively). The vector copy number was 2.6 in the pediatric group and 3.3 in the adolescent group, and 70% versus 82%, respectively, had CD34-positive cells transduced. The estimated daily average area under the curve over the course of 4 days was 4164 

Regarding hematological recovery following infusion, no difference was observed between the 2 subgroups. Absolute neutrophil count of greater than 500 cells/

μL or greater was observed at day 26, while platelets of over 20,000 were observed around day 50. “Natural killer cells were the first to recover, and CD4 cells took the longest to recover,” said Walters. “However, all the lymphocytes had recovered by 6 to 9 months post infusion.”

All patients in the adolescent subgroup achieved transfusion independence with beti-cel, with a duration of ongoing independence of 14.9 months (range, 12.2-21.6). Four of 6 patients in the pediatric subgroup achieved transfusion independence, with a duration of 15.2 months (range, 12.3-17.7).

Moreover, the majority of the total Hb was found to be comprised of HbA787Q in patients who achieved transfusion independence, particularly those in the adolescent group. “The younger group had somewhat lower levels of HbA787Q,” noted Walters.

Investigators also evaluated improvement in ineffective erythropoiesis in patients who achieved transfusion independence. “This was expressed as the level of the soluble transferrin receptor in the blood and absolute reticulocyte count,” explained Walters. “In most of the individuals there were improvements, although not all the patients moved back into the normal range.”

The safety profile of beti-cel was as expected following myeloablative busulfan, noted Walters. The most frequently reported non-hematologic grade 3 or higher toxicities included stomatitis (58%), febrile neutropenia (50%), and decreased appetite (21%). Serious adverse effects (AEs) included pyrexia (13%), febrile neutropenia (8%), and neutropenia (8%).

Toxicities determined to potentially be associated with the gene therapy were grade 1 tachycardia (n = 1) and grade 1 abdominal pain (n = 2) on the day of infusion and grade 3 thrombocytopenia (n = 1) following infusion, although this was not determined to be a serious case. Veno-occlusive liver disease was treated with defibrotide in 3 patients; although all cases resolved, 2 of these cases were determined to be serious.

No graft failure was observed, and all participants were alive at last follow-up, Walters concluded.

1. Walters MC, Kwiatkowski JL, Porter JB, et al. Safety and efficacy in pediatric patients with transfusion-dependent β-thalassemia (TDT) receiving betibeglogene autotemcel (beti-cel; LentiGlobin for β-thalassemia) gene therapy in the phase 3 HGB-207 (Northstar-2) and HGB-212 (Northstar-3) studies. Presented at: 2021 Transplantation & Cellular Therapy Meetings; February 8-12, 2021; Virtual. Abstract 122. 

2. Zynteglo: betibeglogene autotemcel. bluebird bio. Accessed February 10, 2021. 

Results from 2 phase 3 clinical trials showed that use of the investigational gene cell therapy betibeglogene autotemcel led to durable transfusion independence in 87% of pediatric patients under the age of 18 years with transfusion-dependent beta-thalassemia.

Beti-Cel Shows Good Activity in Transfusion-Dependent Children With Beta-Thalassemia

A post-hoc analysis of the practice-changing TRANSCEND NHL 001 trial (NCT02631044) revealed that exposure to anti-CD19 therapy in patients with relapsed/refractory large B-cell lymphoma (LBCL), did not impact response to lisocabtagene maraleucel (liso-cel; Breyanzi).

Data were presented during the 2021 Transplantation & Cellular Therapy Meeting and showed that among 12 patients who had previously received anti-CD19 therapy, 2 patients achieved a complete response (CR) as their best response to that treatment, 3 patients reported a partial response (PR), and 1 achieved stable disease. Five patients experienced disease progression, while 1 patient’s response status was unknown.

Results from the analysis showed that 92% (n = 11/12) experienced an objective response to liso-cel per independent review committee (IRC) assessment and Lugano criteria; this included 6 CRs (50%) and 5 PRs with the CAR T-cell therapy. Moreover, 5 patients experienced a duration of response (DOR) to liso-cel of 9 months or longer (range, 0.8-27.4), with 4 patients continuing to respond at the time of data cutoff.

The response rates reported in this subgroup proved to be comparable to those observed in the overall TRANSCEND NHL 001 study population. Of the 256 patients determined to be efficacy evaluable, which included those who were given at least 1 dose of liso-cel and had PET-positive disease per IRC, the objective response rate was 73% (95% CI, 66.8%-78.0%), with a CR rate of 53% (95% CI, 46.8%-59.4%).2 The median DOR had not been reached (95% CI, 8.6–not reached [NR]). Moreover, the median progression-free survival (PFS) was 6.8 months in this population (95% CI, 3.3-14.1) and the median overall survival (OS) was 21.1 months (95% CI, 13.3-NR).

“In this post-hoc analysis of a small subset of patients from TRANSCEND, patient response to liso-cel and liso-cel pharmacokinetics were not impacted by prior exposure to anti-CD19 therapy,” Scott R. Solomon, MD, of the Blood and Marrow Transplant Program, Leukemia and Cellular Immunotherapy Program at the Northside Hospital Cancer Institute, and colleagues, wrote in a poster highlighting the data. “Additional analyses on a larger number of patients with prior anti-CD19 therapy are warranted to confirm these findings.”

An investigational, CD19-targeted, defined composition, 4-1BB CAR T-cell product, liso-cel is given at equal target doses of CD8 and CD4 T cells; the product has showcased safety and efficacy in patients with aggressive, relapsed/refractory LBCL in the TRANSCEND NHL 001 trial. Data from the trial led to the

February 2021 FDA approval of liso-cel for use in adult patients with certain types of large B-cell lymphoma

 who have not responded to, or who have relapsed after, at least 2 other types of systemic treatment.

The multicenter, pivotal, phase 1 trial enrolled adult patients aged 18 years or older with relapsed/refractory LBCL; this included those with diffuse large B-cell lymphoma (DLBCL); high-grade B-cell lymphoma with rearrangements of 

, or both; DLBCL transformed from an indolent lymphoma; primary mediastinal B-cell lymphoma; and follicular lymphoma. To be eligible for enrollment, patients had to have an ECOG performance status of 0-2, creatinine clearance of greater than 30 mL/min/1.73 m2, and a left ventricular ejection fraction 

Those who underwent prior hematopoietic stem cell transplantation and those with secondary central nervous system lymphoma were permitted. Notably, no lower threshold for absolute lymphocyte count, absolute neutrophil count, platelets, or hemoglobin, were established.

In the trial, patients were screened and then underwent leukapheresis where bridging therapy was permitted while the product was being manufactured. Once disease was reconfirmed via PET imaging, patients went on to receive lymphodepleting chemotherapy with fludarabine at 30 mg/m2 and cytarabine at 300 mg/m2, delivered over the course of 3 days. Two to 7 days after the chemotherapy, patients received liso-cel.

A total of 269 participants were assigned to 1 of 3 target dose levels of the CAR T-cell product: 50 × 106 CAR T cells (1 or 2 doses), 100 × 106, and 150 × 106; this was given as a sequential infusion of 2 components, CD8 and CD4 CAR T cells, at equal target doses.

The co-primary end points of the trial included adverse effects (AEs), dose-limiting toxicities, and ORR per Lugano criteria and IRC. Key secondary end points comprised CR rate by IRC, DOR, PFS, OS, and cellular kinetics.

For the post-hoc analysis, investigators looked at a subset of patients from the trial who had previously received CD19-targeted therapy before liso-cel to evaluate impact of the CAR T-cell product on safety and efficacy outcomes, as well as cellular kinetics.

The median age of the 12 patients in the subgroup of interest was 60.5 years, and 83% were male. Half of the patients had an ECOG performance status of 0, while the remainder had a status of 1. The median number of previous lines of treatment was 4. Fifty-eight percent of patients previously underwent transplantation and 67% were refractory to chemotherapy. Regarding histology, 58% had DLBCL not otherwise specified, 33% had DLBCL that was transformed from follicular lymphoma, and 8% had high-grade B-cell lymphoma.

Additional data showed that previous anti-CD19 therapy did not impact cellular kinetic parameters. Liso-cel demonstrated long-term persistence at 3 months in the majority, or 83% (n = 5/6), of those who received prior CD19-targeted treatment; persistence at 1 year was observed in 50% of patients (n = 2/4), which was comparable to those who did not receive previous CD19-targeted treatment.

Regarding safety, all patients in this subgroup experienced treatment-emergent AEs (TEAEs), 58% (n = 7) of which were grade 3 or higher. The most reported grade 3 or higher TEAEs included neutropenia (58%), thrombocytopenia (42%), and anemia (33%). Sixty-seven percent of patients reported all-grade cytokine release syndrome (CRS) and 42% experienced all-grade neurological effects with liso-cel. However, all toxicity rates proved to be comparable to those experienced by the overall study population and all CRS or neurological effects were either grade 1 or 2.

“These findings suggest that liso-cel can be considered for the treatment of patients who have received prior anti-CD19 therapies,” concluded Solomon.

1. Solomon S, Mehta A, Abramson JS, et al. Experience of prior anti-CD19 therapy in patients with relapsed or refractory large B-cell lymphoma receiving lisocabtagene maraleucel (liso-cel), an investigational anti-CD19 chimeric antigen receptor T cell product. Presented at: 2021 Transplantation & Cellular Therapy Meeting; February 9-13, 2021; Virtual.

2. Abramson JS, Palomba ML, Gordon LI, et al. Lisocabtagene maraleucel for patients with relapsed or refractory large B-cell lymphomas (TRANSCEND NHL 001): a multicentre seamless design study. 

. 2020;396(10254):839-852. doi:10.1016/S0140-6736(20)31366-0

A post-hoc analysis of the practice-changing TRANSCEND NHL 001 trial revealed that exposure to anti-CD19 therapy in patients with relapsed/refractory large B-cell lymphoma, did not impact response to lisocabtagene maraleucel.

Responses to Liso-Cel Not Influenced by Prior Treatment With Anti-CD19 Agents in R/R Large B-Cell Lymphoma

-mutated non–small cell lung cancer (NSCLC), adjuvant treatment with osimertinib (Tagrisso) in the pivotal phase 3 ADAURA trial (NCT02511106) led to improvement in disease-free survival (DFS), irrespective of previous adjuvant chemotherapy received or disease stage, according to results presented during the International Association for the Study of Lung Cancer 2020 World Conference on Lung Cancer (WCLC).

In the overall patient population, adjuvant osimertinib resulted in an 84% reduction in the risk of disease recurrence or death in patients who had previously received adjuvant chemotherapy (HR, 0.16; 95% CI, 0.10-0.26); the reduction was slightly lower, at 77% (HR, 0.23; 95% CI, 0.13-0.40), in those who had not received chemotherapy. Notably, the DFS benefit achieved with adjuvant osimertinib proved to be comparable across all stages of disease examined.

“The overwhelming DFS benefit in patients in ADAURA already supported the role of [osimertinib] as a pioneering therapy in the adjuvant treatment of 

-mutated NSCLC,” principal investigator of the trial Yi-Long Wu, MD, FACS, tenured professor of the Lung Cancer Institute at Guangdong Provincial People’s Hospital and Academy of Medical Sciences, stated in a press release. “The latest analysis shows the magnitude of that benefit is consistent with or without prior adjuvant chemotherapy, and regardless of disease stage, reinforcing the critical role of [osimertinib] in this setting.”

The phase 3 trial enrolled a total of 682 patients with completely resected stage IB, II, IIIA NSCLC who had and had not received adjuvant chemotherapy. To be eligible for enrollment, patients had to be at least 18 years of age (20 years or older if from Japan/Taiwan), have a World Health Organization (WHO) performance status of 0 or 1, have confirmed primary nonsquamous disease and an 

 exon 19 deletion or exon 21 L858R deletion.

Participants were stratified based on disease stage (IB vs II vs IIIA), 

 mutation (exon 19 deletion vs exon 21 L858R), and race (Asian vs non-Asian). In the trial, patients were randomized 1:1 to receive either osimertinib at a once-daily dose of 80 mg (n = 339) or once-daily placebo (n = 343). Patients continued to receive treatment until either disease recurrence, treatment was completed, or discontinuation criterion were met.

The primary objective of the trial was DFS per investigator assessment, while key secondary end points comprised DFS in the overall population; DFS at 2, 3, 4, and 5 years; overall survival, safety, and health-related quality of life (QoL).

The median age of study participants was 63 years; 30% were male and 64% were Asian. Approximately 72% of patients were never smokers and the majority(64%) had a WHO performance status of 0. Fifty-five percent of patients had tumors that harbored an 

 exon 19 deletion, while 45% had an exon 21 L858R deletion. Sixty percent of patients had previously received adjuvant chemotherapy. Notably, younger patients and those with more advanced disease were more likely to have received prior adjuvant chemotherapy, and treatment with chemotherapy did not vary based on a patient’s performance status.

Early results from the trial presented during the 2020 ASCO Virtual Scientific Program showed that adjuvant osimertinib resulted in a statistically significant improvement in DFS in patients with stage IB/II/IIA 

-mutated NSCLC. The median DFS, per investigator assessment, had not been reached with osimertinib versus 19.6 months with placebo (HR, 0.17; 95% CI, 0.12-0.23; 

 In the overall population, the median DFS also had not been reached in those who received the EGFR TKI versus 27.5 months with placebo (HR, 0.20; 95% CI, 0.15-0.27; 

<.0001). These data resulted in the December 2020 

FDA approval of osimertinib as adjuvant therapy in select patients with 

Updated data presented during the 2020 ESMO Virtual Congress showed that treatment with adjuvant osimertinib also resulted in a clinically meaningful improvement in central nervous system (CNS) DFS compared with placebo (HR, 0.18; 95% CI, 0.10-0.33; 

<.0001); this translated to an 82% reduction in the risk of CNS disease recurrence or death.

 The median CNS DFS in the overall population had not yet been reached in the investigative arm compared with 48.2 months in the control arm.

Additionally, CNS disease recurrence was found to be less likely with the EGFR TKI versus placebo, with a conditional probability of less than 1% at 18 months with osimertinib.

Additional results presented during the 2020 WCLC showed that in patients who had previously received adjuvant chemotherapy, the DFS HR was not computable in those with stage IB disease, 0.15 (95% CI, 0.06-0.32) in those with stage II disease, and 0.13 (95% CI, 0.06-0.23) in those with stage IIIA disease. In the subgroup of patients who did not previously receive chemotherapy, the DFS HR was 0.38 (95% CI, 0.15-0.88) in those with stage IB disease, 0.20 (95% CI, 0.07-0.52) in those with stage II disease, and 0.10 (95% CI, 0.02-0.29) in those with stage IIIA disease.

Moreover, data from a separate exploratory post-hoc analysis of patient-reported outcomes in the trial demonstrated that those who received the EGFR TKI maintained their QoL, with no clinically meaningful differences in physical or mental health measures observed between the 2 treatment arms.

Regarding safety, the data proved to be consistent with what had previously been reported with osimertinib. Per investigator assessment, all-grade toxicities that were grade 3 or higher in severity were reported in 20% of the patients who received osimertinib versus 13% of those who were given placebo.

1. Tagrisso extended disease-free survival regardless of prior adjuvant chemotherapy in early-stage EGFR-mutated lung cancer. News release. AstraZeneca. January 29, 2021. Accessed January 29, 2021. 

2. Tsuboi M, Wu Y-L, He J, et al. Osimertinib adjuvant therapy in patients with resected EGFR mutated NSCLC (ADAURA): CNS disease recurrence. 

. 2020;31(suppl 6):S1378. doi:10.1016/j.annonc.2020.10.349

3. Herbst RS, Tsuboi M, John T, et al. Osimertinib as adjuvant therapy in patients (pts) with stage IB-IIIA EGFR mutation positive (EGFRm) NSCLC after complete tumor resection: ADAURA. 

. 2020;38(suppl 15):LBA5. doi:10.1200/JCO.2020.38.18_suppl.LBA5

In patients with EGFR-mutated non–small cell lung cancer, adjuvant treatment with osimertinib in the pivotal phase 3 ADAURA trial led to improvement in disease-free survival, irrespective of previous adjuvant chemotherapy received or disease stage.

Kristi Rosa | Authors

Articles

OS Benefit Suggested for Frontline IO Versus TKIs in Metastatic Non–Clear Cell RCC

Beti-Cel Shows Good Activity in Transfusion-Dependent Children With Beta-Thalassemia

Responses to Liso-Cel Not Influenced by Prior Treatment With Anti-CD19 Agents in R/R Large B-Cell Lymphoma

DFS Prolonged With Adjuvant Osimertinib Despite Prior Adjuvant Chemo in EGFR+ NSCLC