Lung Cancer

In a European Society for Medical Oncology Virtual Plenary session, Dr Paz-Ares and colleagues presented interim analysis of the PEARLS/KEYNOTE-091 study of adjuvant pembrolizumab. In this triple-blind phase 3 trial, 1177 patients with stage IB (tumor ≥ 4 cm) to IIIA non–small cell lung cancer (NSCLC) (per American Joint Committee on Cancer [AJCC], version 7) were randomly assigned to receive pembrolizumab vs placebo. The dual primary endpoints were disease-free survival (DFS) in the overall population and in the population with high programmed death-ligand 1 (PD-L1) (tumor proportion score [TPS] ≥ 50%). The study met its primary endpoint where improved DFS was observed in the overall population that included lung cancers, whether they were PD-L1–negative (TPS = 0%) or –positive (TPS  ≥ 1%) (53.6 months in the pembrolizumab group vs 42.0 months in the placebo group [hazard ratio (HR) 0.76; P = .0014]). Overall survival data are not yet clear. Of note, in the interim analysis presented, the subset of patients with high PD-L1 NSCLC (TPS ≥ 50%) did not show a DFS benefit whereas in other adjuvant and neoadjuvant studies, such as IMpower010 and CheckMate 816, the subset of high PD-L1 patients appeared to derive the most benefit. The results from the high PD-L1 subset and other subsets may change with future updated analyses as more events occur. The major co-primary endpoint was clearly met with the overall population clearly showing a positive DFS benefit. The results of the PEARLS trial adds to the current landscape of systemic treatment of early-stage NSCLC where neoadjuvant chemotherapy plus nivolumab is US Food and Drug Administration (FDA)–approved for stage IB (≥ 4 cm) to IIIA resected NSCLC regardless of level of PD-L1 expression, as is adjuvant atezolizumab after consideration of adjuvant chemotherapy in patients that are PD-L1–positive (≥ 1%) on the basis of a DFS benefit observed in this population.^1,2 For the future, it is important to see if the DFS benefit observed in these studies translates into a meaningful overall survival benefit.

Plasma cfDNA Levels as a Prognostic Marker in ALK+ NSCLC in the ALEX Trial

The ALEX trial is a pivotal global phase 3 randomized control trial that demonstrated superior progression-free survival (PFS) with the next-generation ALK inhibitor alectinib compared with the first-generation ALK inhibitor crizotinib as first-line treatment of ALK-positive NSCLC (HR 0.43; 95% CI 0.32-0.58; median PFS 34.8 vs 10.9 months crizotinib).³ In a study recently published in Clinical Cancer Research, Dr Dziadziuszko and colleagues retrospectively assessed the prognostic value of baseline cell-free DNA (cfDNA) levels in patients treated in the ALEX trial. Baseline plasma for cfDNA was quantified by the Foundation ACT next-generation sequencing assay. Clinical outcomes were assessed by quantitative cfDNA level stratified by the median value. In both the alectinib and crizotinib treatment arms, patients with cfDNA levels above the median were more likely to experience disease progression (alectinib adjusted HR 2.04; 95% CI 1.07-3.89; P = .03 and crizotinib adjusted HR 1.83; 95% CI 1.11-3.00, P = .016). Though survival data are incomplete, the study also suggested survival probability was lower when baseline cfDNA was above the median in both the alectinib and crizotinib treatment arms. Regardless of cfDNA levels, PFS was improved with alectinib compared with crizotinib. Previous studies have shown the value of cfDNA analysis at the time of progression to guide further treatment and target resistance mechanisms to ALK tyrosine kinase inhibitors (TKI), such as G1202R, or bypass tract pathways, such as MET amplification.^4,5 Assessment of the EML4-ALK variant type (V1 vs V3) has been shown to associate with certain types of resistance mechanisms (ie, on target ALK mutations, such as G1202R in V3) and clinical activity of specific ALK TKI (V3 > V1 for PFS with lorlatinib).⁶ This study examining baseline cfDNA levels and clinical outcomes on the ALEX trial shows the potential utility of baseline cfDNA levels as a prognostic factor for ALK TKI.

Lorlatinib in ROS1-Rearranged NSCLC After Progression on Prior ROS1 TKI

ROS1 rearrangements represent about 1.5% of lung adenocarcinoma. In advanced disease, both crizotinib and entrectinib are FDA-approved as agents targeting ROS1 with robust PFS. The third-generation TKI lorlatinib is approved and has substantial activity in ALK-rearranged NSCLC. In a recently published retrospective real-world cohort study by Girard and colleagues (LORLATU), 80 patients with ROS1-rearranged NSCLC were treated with lorlatinib as second-line treatment or beyond and after failure on at least one prior ROS1 TKI. Median PFS was 7.1 months (95% CI 5.0-9.9) and median overall survival was 19.6 months (95% CI 12.3-27.5). The overall response rate was 45% and the disease control rate was 82%. The central nervous system response rate was 72%. There were no new safety signals. This retrospective cohort study demonstrates that lorlatinib is a major targeted therapy treatment option in ROS1-rearranged NSCLC.

Checkmate 816: Neoadjuvant Nivolumab Plus Chemotherapy in Resectable NSCLC

In this open-label, phase 3 trial, 358 patients with stage IB (T ³ 4cm) to IIIA (per AJCC v7) resectable NSCLC were randomized 1:1 to receive nivolumab plus platinum-based chemotherapy or platinum-based chemotherapy alone for three cycles, followed by surgical resection. The primary endpoints were event-free survival (EFS) and pathological complete response (pCR) (0% viable tumor in resected lung and lymph nodes), both evaluated by blinded independent review. The median EFS was significantly increased in the nivolumab plus chemotherapy arm compared to chemotherapy alone: 31.6 months (95% CI 30.2 to not reached) vs 20.8 months (95% CI 14.0 to 26.7) (HR 0.63; 97.38% CI 0.43 to 0.91; P = .005). pCR rate was also increased in the nivolumab plus chemotherapy arm (24.0% vs 2.2%, respectively; odds ratio 13.94; 99% CI 3.49 to 55.75; P < .001). At the first prespecified interim analysis, the hazard ratio for death was 0.57 (99.67% CI 0.30 to 1.07), which currently does not meet the criterion for statistical significance. Of the randomized patients, 83.2% of those in the nivolumab-plus chemotherapy group and 75.4% of those in the chemotherapy-alone group were able to undergo surgery. Grade 3 or 4 treatment-related adverse events occurred in 33.5% of the patients in the nivolumab-plus-chemotherapy group and in 36.9% of those in the chemotherapy-alone group. In an exploratory analysis, EFS was longer in patients with pCR than patients without a pCR. In a subset analysis, patients with high PD-L1 expression (³50%) stood out in terms of particular benefit (HR 0.24, 95% CI 0.10–0.61). The Checkmate 816 trial is a landmark study. Neoadjuvant nivolumab plus chemotherapy represents a new standard of care in the systemic treatment of resectable NSCLC that is at a stage that warrants systemic treatment. It is FDA approved regardless of PD-L1 expression level including PD-L1 negative (0%) patients.² Adjuvant atezolizumab after adjuvant chemotherapy is also an FDA-approved treatment option for patients that are PD-L1 positive (³1%) based upon the IMpower 010 study.¹ It will be important to assess the overall survival benefit as the trial data matures, which seems to be trending in the right direction. Additional neoadjuvant clinical trials with chemoimmunotherapy have completed accrual and some of these trials also continued PD-(L)1 immune checkpoint inhibitor therapy in the adjuvant setting after surgery. An important question for the future is if combination of PD-(L)1 immune checkpoint blockade with chemotherapy in the neoadjuvant setting along with continuation of immunotherapy in the adjuvant setting post-surgery will further improve clinical outcomes.

References

1. Felip E, Altorki N, Zhou C, et al. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet. 2021;398(10308):1344-57. Doi: 10.1016/S0140-6736(21)02098-5  Source

2. Forde PM, Spicer J, Lu S, et al. Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer. N Engl J Med. April 11, 2022. Doi: 10.1056/NEJMoa2202170 Source
    
3. Mok T, Camige DR, Gadgeel SM, et al. Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study. Ann Oncol. 2020;31:1056-1064. Doi: 10.1016/j.annonc.2020.04.478 Source

4. Shaw AT, Solomon BJ, Chiari R, et al. Lorlatinib in advanced ROS1-positive non-small-cell lung cancer: a multicentre, open-label, single-arm, phase 1-2 trial. Lancet Oncol. 2019;20:1691-1701. Doi: 10.1016/S1470-2045(19)30655-2 Source
    
5. Lawrence MN, Tamen RM, Martinez P, et al. SPACEWALK: A remote participation study of ALK resistance leveraging plasma cell-free DNA genotyping. JTO Clin Res Rep. 2021;2:100151. Doi: 10.1016/j.jtocrr.2021.100151 Source
    
6. Lin JJ, Zhu VW, Yoda S, et al. Impact of EML4-ALK variant on resistance mechanisms and clinical outcomes in ALK-positive lung cancer. J Clin Oncol. 2018;36:1199-1206. Doi: 10.1200/JCO.2017.76.2294 Source

In a European Society for Medical Oncology Virtual Plenary session, Dr Paz-Ares and colleagues presented interim analysis of the PEARLS/KEYNOTE-091 study of adjuvant pembrolizumab. In this triple-blind phase 3 trial, 1177 patients with stage IB (tumor ≥ 4 cm) to IIIA non–small cell lung cancer (NSCLC) (per American Joint Committee on Cancer [AJCC], version 7) were randomly assigned to receive pembrolizumab vs placebo. The dual primary endpoints were disease-free survival (DFS) in the overall population and in the population with high programmed death-ligand 1 (PD-L1) (tumor proportion score [TPS] ≥ 50%). The study met its primary endpoint where improved DFS was observed in the overall population that included lung cancers, whether they were PD-L1–negative (TPS = 0%) or –positive (TPS  ≥ 1%) (53.6 months in the pembrolizumab group vs 42.0 months in the placebo group [hazard ratio (HR) 0.76; P = .0014]). Overall survival data are not yet clear. Of note, in the interim analysis presented, the subset of patients with high PD-L1 NSCLC (TPS ≥ 50%) did not show a DFS benefit whereas in other adjuvant and neoadjuvant studies, such as IMpower010 and CheckMate 816, the subset of high PD-L1 patients appeared to derive the most benefit. The results from the high PD-L1 subset and other subsets may change with future updated analyses as more events occur. The major co-primary endpoint was clearly met with the overall population clearly showing a positive DFS benefit. The results of the PEARLS trial adds to the current landscape of systemic treatment of early-stage NSCLC where neoadjuvant chemotherapy plus nivolumab is US Food and Drug Administration (FDA)–approved for stage IB (≥ 4 cm) to IIIA resected NSCLC regardless of level of PD-L1 expression, as is adjuvant atezolizumab after consideration of adjuvant chemotherapy in patients that are PD-L1–positive (≥ 1%) on the basis of a DFS benefit observed in this population.^1,2 For the future, it is important to see if the DFS benefit observed in these studies translates into a meaningful overall survival benefit.

Plasma cfDNA Levels as a Prognostic Marker in ALK+ NSCLC in the ALEX Trial

The ALEX trial is a pivotal global phase 3 randomized control trial that demonstrated superior progression-free survival (PFS) with the next-generation ALK inhibitor alectinib compared with the first-generation ALK inhibitor crizotinib as first-line treatment of ALK-positive NSCLC (HR 0.43; 95% CI 0.32-0.58; median PFS 34.8 vs 10.9 months crizotinib).³ In a study recently published in Clinical Cancer Research, Dr Dziadziuszko and colleagues retrospectively assessed the prognostic value of baseline cell-free DNA (cfDNA) levels in patients treated in the ALEX trial. Baseline plasma for cfDNA was quantified by the Foundation ACT next-generation sequencing assay. Clinical outcomes were assessed by quantitative cfDNA level stratified by the median value. In both the alectinib and crizotinib treatment arms, patients with cfDNA levels above the median were more likely to experience disease progression (alectinib adjusted HR 2.04; 95% CI 1.07-3.89; P = .03 and crizotinib adjusted HR 1.83; 95% CI 1.11-3.00, P = .016). Though survival data are incomplete, the study also suggested survival probability was lower when baseline cfDNA was above the median in both the alectinib and crizotinib treatment arms. Regardless of cfDNA levels, PFS was improved with alectinib compared with crizotinib. Previous studies have shown the value of cfDNA analysis at the time of progression to guide further treatment and target resistance mechanisms to ALK tyrosine kinase inhibitors (TKI), such as G1202R, or bypass tract pathways, such as MET amplification.^4,5 Assessment of the EML4-ALK variant type (V1 vs V3) has been shown to associate with certain types of resistance mechanisms (ie, on target ALK mutations, such as G1202R in V3) and clinical activity of specific ALK TKI (V3 > V1 for PFS with lorlatinib).⁶ This study examining baseline cfDNA levels and clinical outcomes on the ALEX trial shows the potential utility of baseline cfDNA levels as a prognostic factor for ALK TKI.

Lorlatinib in ROS1-Rearranged NSCLC After Progression on Prior ROS1 TKI

ROS1 rearrangements represent about 1.5% of lung adenocarcinoma. In advanced disease, both crizotinib and entrectinib are FDA-approved as agents targeting ROS1 with robust PFS. The third-generation TKI lorlatinib is approved and has substantial activity in ALK-rearranged NSCLC. In a recently published retrospective real-world cohort study by Girard and colleagues (LORLATU), 80 patients with ROS1-rearranged NSCLC were treated with lorlatinib as second-line treatment or beyond and after failure on at least one prior ROS1 TKI. Median PFS was 7.1 months (95% CI 5.0-9.9) and median overall survival was 19.6 months (95% CI 12.3-27.5). The overall response rate was 45% and the disease control rate was 82%. The central nervous system response rate was 72%. There were no new safety signals. This retrospective cohort study demonstrates that lorlatinib is a major targeted therapy treatment option in ROS1-rearranged NSCLC.

Checkmate 816: Neoadjuvant Nivolumab Plus Chemotherapy in Resectable NSCLC

In this open-label, phase 3 trial, 358 patients with stage IB (T ³ 4cm) to IIIA (per AJCC v7) resectable NSCLC were randomized 1:1 to receive nivolumab plus platinum-based chemotherapy or platinum-based chemotherapy alone for three cycles, followed by surgical resection. The primary endpoints were event-free survival (EFS) and pathological complete response (pCR) (0% viable tumor in resected lung and lymph nodes), both evaluated by blinded independent review. The median EFS was significantly increased in the nivolumab plus chemotherapy arm compared to chemotherapy alone: 31.6 months (95% CI 30.2 to not reached) vs 20.8 months (95% CI 14.0 to 26.7) (HR 0.63; 97.38% CI 0.43 to 0.91; P = .005). pCR rate was also increased in the nivolumab plus chemotherapy arm (24.0% vs 2.2%, respectively; odds ratio 13.94; 99% CI 3.49 to 55.75; P < .001). At the first prespecified interim analysis, the hazard ratio for death was 0.57 (99.67% CI 0.30 to 1.07), which currently does not meet the criterion for statistical significance. Of the randomized patients, 83.2% of those in the nivolumab-plus chemotherapy group and 75.4% of those in the chemotherapy-alone group were able to undergo surgery. Grade 3 or 4 treatment-related adverse events occurred in 33.5% of the patients in the nivolumab-plus-chemotherapy group and in 36.9% of those in the chemotherapy-alone group. In an exploratory analysis, EFS was longer in patients with pCR than patients without a pCR. In a subset analysis, patients with high PD-L1 expression (³50%) stood out in terms of particular benefit (HR 0.24, 95% CI 0.10–0.61). The Checkmate 816 trial is a landmark study. Neoadjuvant nivolumab plus chemotherapy represents a new standard of care in the systemic treatment of resectable NSCLC that is at a stage that warrants systemic treatment. It is FDA approved regardless of PD-L1 expression level including PD-L1 negative (0%) patients.² Adjuvant atezolizumab after adjuvant chemotherapy is also an FDA-approved treatment option for patients that are PD-L1 positive (³1%) based upon the IMpower 010 study.¹ It will be important to assess the overall survival benefit as the trial data matures, which seems to be trending in the right direction. Additional neoadjuvant clinical trials with chemoimmunotherapy have completed accrual and some of these trials also continued PD-(L)1 immune checkpoint inhibitor therapy in the adjuvant setting after surgery. An important question for the future is if combination of PD-(L)1 immune checkpoint blockade with chemotherapy in the neoadjuvant setting along with continuation of immunotherapy in the adjuvant setting post-surgery will further improve clinical outcomes.

References

1. Felip E, Altorki N, Zhou C, et al. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet. 2021;398(10308):1344-57. Doi: 10.1016/S0140-6736(21)02098-5  Source

2. Forde PM, Spicer J, Lu S, et al. Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer. N Engl J Med. April 11, 2022. Doi: 10.1056/NEJMoa2202170 Source
    
3. Mok T, Camige DR, Gadgeel SM, et al. Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study. Ann Oncol. 2020;31:1056-1064. Doi: 10.1016/j.annonc.2020.04.478 Source

4. Shaw AT, Solomon BJ, Chiari R, et al. Lorlatinib in advanced ROS1-positive non-small-cell lung cancer: a multicentre, open-label, single-arm, phase 1-2 trial. Lancet Oncol. 2019;20:1691-1701. Doi: 10.1016/S1470-2045(19)30655-2 Source
    
5. Lawrence MN, Tamen RM, Martinez P, et al. SPACEWALK: A remote participation study of ALK resistance leveraging plasma cell-free DNA genotyping. JTO Clin Res Rep. 2021;2:100151. Doi: 10.1016/j.jtocrr.2021.100151 Source
    
6. Lin JJ, Zhu VW, Yoda S, et al. Impact of EML4-ALK variant on resistance mechanisms and clinical outcomes in ALK-positive lung cancer. J Clin Oncol. 2018;36:1199-1206. Doi: 10.1200/JCO.2017.76.2294 Source

In a European Society for Medical Oncology Virtual Plenary session, Dr Paz-Ares and colleagues presented interim analysis of the PEARLS/KEYNOTE-091 study of adjuvant pembrolizumab. In this triple-blind phase 3 trial, 1177 patients with stage IB (tumor ≥ 4 cm) to IIIA non–small cell lung cancer (NSCLC) (per American Joint Committee on Cancer [AJCC], version 7) were randomly assigned to receive pembrolizumab vs placebo. The dual primary endpoints were disease-free survival (DFS) in the overall population and in the population with high programmed death-ligand 1 (PD-L1) (tumor proportion score [TPS] ≥ 50%). The study met its primary endpoint where improved DFS was observed in the overall population that included lung cancers, whether they were PD-L1–negative (TPS = 0%) or –positive (TPS  ≥ 1%) (53.6 months in the pembrolizumab group vs 42.0 months in the placebo group [hazard ratio (HR) 0.76; P = .0014]). Overall survival data are not yet clear. Of note, in the interim analysis presented, the subset of patients with high PD-L1 NSCLC (TPS ≥ 50%) did not show a DFS benefit whereas in other adjuvant and neoadjuvant studies, such as IMpower010 and CheckMate 816, the subset of high PD-L1 patients appeared to derive the most benefit. The results from the high PD-L1 subset and other subsets may change with future updated analyses as more events occur. The major co-primary endpoint was clearly met with the overall population clearly showing a positive DFS benefit. The results of the PEARLS trial adds to the current landscape of systemic treatment of early-stage NSCLC where neoadjuvant chemotherapy plus nivolumab is US Food and Drug Administration (FDA)–approved for stage IB (≥ 4 cm) to IIIA resected NSCLC regardless of level of PD-L1 expression, as is adjuvant atezolizumab after consideration of adjuvant chemotherapy in patients that are PD-L1–positive (≥ 1%) on the basis of a DFS benefit observed in this population.^1,2 For the future, it is important to see if the DFS benefit observed in these studies translates into a meaningful overall survival benefit.

Plasma cfDNA Levels as a Prognostic Marker in ALK+ NSCLC in the ALEX Trial

The ALEX trial is a pivotal global phase 3 randomized control trial that demonstrated superior progression-free survival (PFS) with the next-generation ALK inhibitor alectinib compared with the first-generation ALK inhibitor crizotinib as first-line treatment of ALK-positive NSCLC (HR 0.43; 95% CI 0.32-0.58; median PFS 34.8 vs 10.9 months crizotinib).³ In a study recently published in Clinical Cancer Research, Dr Dziadziuszko and colleagues retrospectively assessed the prognostic value of baseline cell-free DNA (cfDNA) levels in patients treated in the ALEX trial. Baseline plasma for cfDNA was quantified by the Foundation ACT next-generation sequencing assay. Clinical outcomes were assessed by quantitative cfDNA level stratified by the median value. In both the alectinib and crizotinib treatment arms, patients with cfDNA levels above the median were more likely to experience disease progression (alectinib adjusted HR 2.04; 95% CI 1.07-3.89; P = .03 and crizotinib adjusted HR 1.83; 95% CI 1.11-3.00, P = .016). Though survival data are incomplete, the study also suggested survival probability was lower when baseline cfDNA was above the median in both the alectinib and crizotinib treatment arms. Regardless of cfDNA levels, PFS was improved with alectinib compared with crizotinib. Previous studies have shown the value of cfDNA analysis at the time of progression to guide further treatment and target resistance mechanisms to ALK tyrosine kinase inhibitors (TKI), such as G1202R, or bypass tract pathways, such as MET amplification.^4,5 Assessment of the EML4-ALK variant type (V1 vs V3) has been shown to associate with certain types of resistance mechanisms (ie, on target ALK mutations, such as G1202R in V3) and clinical activity of specific ALK TKI (V3 > V1 for PFS with lorlatinib).⁶ This study examining baseline cfDNA levels and clinical outcomes on the ALEX trial shows the potential utility of baseline cfDNA levels as a prognostic factor for ALK TKI.

Lorlatinib in ROS1-Rearranged NSCLC After Progression on Prior ROS1 TKI

ROS1 rearrangements represent about 1.5% of lung adenocarcinoma. In advanced disease, both crizotinib and entrectinib are FDA-approved as agents targeting ROS1 with robust PFS. The third-generation TKI lorlatinib is approved and has substantial activity in ALK-rearranged NSCLC. In a recently published retrospective real-world cohort study by Girard and colleagues (LORLATU), 80 patients with ROS1-rearranged NSCLC were treated with lorlatinib as second-line treatment or beyond and after failure on at least one prior ROS1 TKI. Median PFS was 7.1 months (95% CI 5.0-9.9) and median overall survival was 19.6 months (95% CI 12.3-27.5). The overall response rate was 45% and the disease control rate was 82%. The central nervous system response rate was 72%. There were no new safety signals. This retrospective cohort study demonstrates that lorlatinib is a major targeted therapy treatment option in ROS1-rearranged NSCLC.

Checkmate 816: Neoadjuvant Nivolumab Plus Chemotherapy in Resectable NSCLC

In this open-label, phase 3 trial, 358 patients with stage IB (T ³ 4cm) to IIIA (per AJCC v7) resectable NSCLC were randomized 1:1 to receive nivolumab plus platinum-based chemotherapy or platinum-based chemotherapy alone for three cycles, followed by surgical resection. The primary endpoints were event-free survival (EFS) and pathological complete response (pCR) (0% viable tumor in resected lung and lymph nodes), both evaluated by blinded independent review. The median EFS was significantly increased in the nivolumab plus chemotherapy arm compared to chemotherapy alone: 31.6 months (95% CI 30.2 to not reached) vs 20.8 months (95% CI 14.0 to 26.7) (HR 0.63; 97.38% CI 0.43 to 0.91; P = .005). pCR rate was also increased in the nivolumab plus chemotherapy arm (24.0% vs 2.2%, respectively; odds ratio 13.94; 99% CI 3.49 to 55.75; P < .001). At the first prespecified interim analysis, the hazard ratio for death was 0.57 (99.67% CI 0.30 to 1.07), which currently does not meet the criterion for statistical significance. Of the randomized patients, 83.2% of those in the nivolumab-plus chemotherapy group and 75.4% of those in the chemotherapy-alone group were able to undergo surgery. Grade 3 or 4 treatment-related adverse events occurred in 33.5% of the patients in the nivolumab-plus-chemotherapy group and in 36.9% of those in the chemotherapy-alone group. In an exploratory analysis, EFS was longer in patients with pCR than patients without a pCR. In a subset analysis, patients with high PD-L1 expression (³50%) stood out in terms of particular benefit (HR 0.24, 95% CI 0.10–0.61). The Checkmate 816 trial is a landmark study. Neoadjuvant nivolumab plus chemotherapy represents a new standard of care in the systemic treatment of resectable NSCLC that is at a stage that warrants systemic treatment. It is FDA approved regardless of PD-L1 expression level including PD-L1 negative (0%) patients.² Adjuvant atezolizumab after adjuvant chemotherapy is also an FDA-approved treatment option for patients that are PD-L1 positive (³1%) based upon the IMpower 010 study.¹ It will be important to assess the overall survival benefit as the trial data matures, which seems to be trending in the right direction. Additional neoadjuvant clinical trials with chemoimmunotherapy have completed accrual and some of these trials also continued PD-(L)1 immune checkpoint inhibitor therapy in the adjuvant setting after surgery. An important question for the future is if combination of PD-(L)1 immune checkpoint blockade with chemotherapy in the neoadjuvant setting along with continuation of immunotherapy in the adjuvant setting post-surgery will further improve clinical outcomes.

References

1. Felip E, Altorki N, Zhou C, et al. Adjuvant atezolizumab after adjuvant chemotherapy in resected stage IB-IIIA non-small-cell lung cancer (IMpower010): a randomised, multicentre, open-label, phase 3 trial. Lancet. 2021;398(10308):1344-57. Doi: 10.1016/S0140-6736(21)02098-5  Source

2. Forde PM, Spicer J, Lu S, et al. Neoadjuvant nivolumab plus chemotherapy in resectable lung cancer. N Engl J Med. April 11, 2022. Doi: 10.1056/NEJMoa2202170 Source
    
3. Mok T, Camige DR, Gadgeel SM, et al. Updated overall survival and final progression-free survival data for patients with treatment-naive advanced ALK-positive non-small-cell lung cancer in the ALEX study. Ann Oncol. 2020;31:1056-1064. Doi: 10.1016/j.annonc.2020.04.478 Source

4. Shaw AT, Solomon BJ, Chiari R, et al. Lorlatinib in advanced ROS1-positive non-small-cell lung cancer: a multicentre, open-label, single-arm, phase 1-2 trial. Lancet Oncol. 2019;20:1691-1701. Doi: 10.1016/S1470-2045(19)30655-2 Source
    
5. Lawrence MN, Tamen RM, Martinez P, et al. SPACEWALK: A remote participation study of ALK resistance leveraging plasma cell-free DNA genotyping. JTO Clin Res Rep. 2021;2:100151. Doi: 10.1016/j.jtocrr.2021.100151 Source
    
6. Lin JJ, Zhu VW, Yoda S, et al. Impact of EML4-ALK variant on resistance mechanisms and clinical outcomes in ALK-positive lung cancer. J Clin Oncol. 2018;36:1199-1206. Doi: 10.1200/JCO.2017.76.2294 Source

The National Comprehensive Cancer Network (NCCN) has recommended a fifth COVID-19 mRNA shot for people who are immunocompromised, including many with cancer or a history of cancer.

A fifth shot of an mRNA vaccine represents a second booster, the group explained, because the primary mRNA immunization series for immunocompromised individuals involves three doses of either the Pfizer or Moderna vaccine.

The update, issued today, comes from the NCCN’s Advisory Committee on COVID-19 Vaccination and Pre-exposure Prophylaxis, which released its first vaccine guidelines for patients with cancer in January 2021. The NCCN has issued numerous updates since then as information about the virus and vaccines has evolved. 

“We know a lot more about COVID-19 and the vaccines now, and we can use that knowledge to minimize the confusion and enhance the protection we can offer to our immunocompromised patients,” said advisory committee co-leader Lindsey Baden, MD, an infectious diseases specialist at the Dana-Farber Cancer Institute, Boston.

The latest iteration of the NCCN’s COVID guidelines includes an update for patients who initially received Johnson & Johnson’s single-shot vaccine, including a recommendation that patients receive an mRNA vaccine for both the first and second booster.

The group also updated dosing recommendations for pre-exposure prevention with tixagevimab plus cilgavimab (Evusheld, AstraZeneca), suggesting 300 mg of each monoclonal antibody instead of 150 mg, based on in vitro activity against Omicron variants.

The group noted that the Moderna and Pfizer shots can be used interchangeably for boosters.

“The NCCN Committee considers both homologous and heterologous boosters to be appropriate options,” the experts wrote.

A version of this article first appeared on Medscape.com.

The National Comprehensive Cancer Network (NCCN) has recommended a fifth COVID-19 mRNA shot for people who are immunocompromised, including many with cancer or a history of cancer.

A fifth shot of an mRNA vaccine represents a second booster, the group explained, because the primary mRNA immunization series for immunocompromised individuals involves three doses of either the Pfizer or Moderna vaccine.

The update, issued today, comes from the NCCN’s Advisory Committee on COVID-19 Vaccination and Pre-exposure Prophylaxis, which released its first vaccine guidelines for patients with cancer in January 2021. The NCCN has issued numerous updates since then as information about the virus and vaccines has evolved. 

“We know a lot more about COVID-19 and the vaccines now, and we can use that knowledge to minimize the confusion and enhance the protection we can offer to our immunocompromised patients,” said advisory committee co-leader Lindsey Baden, MD, an infectious diseases specialist at the Dana-Farber Cancer Institute, Boston.

The latest iteration of the NCCN’s COVID guidelines includes an update for patients who initially received Johnson & Johnson’s single-shot vaccine, including a recommendation that patients receive an mRNA vaccine for both the first and second booster.

The group also updated dosing recommendations for pre-exposure prevention with tixagevimab plus cilgavimab (Evusheld, AstraZeneca), suggesting 300 mg of each monoclonal antibody instead of 150 mg, based on in vitro activity against Omicron variants.

The group noted that the Moderna and Pfizer shots can be used interchangeably for boosters.

“The NCCN Committee considers both homologous and heterologous boosters to be appropriate options,” the experts wrote.

A version of this article first appeared on Medscape.com.

The National Comprehensive Cancer Network (NCCN) has recommended a fifth COVID-19 mRNA shot for people who are immunocompromised, including many with cancer or a history of cancer.

A fifth shot of an mRNA vaccine represents a second booster, the group explained, because the primary mRNA immunization series for immunocompromised individuals involves three doses of either the Pfizer or Moderna vaccine.

The update, issued today, comes from the NCCN’s Advisory Committee on COVID-19 Vaccination and Pre-exposure Prophylaxis, which released its first vaccine guidelines for patients with cancer in January 2021. The NCCN has issued numerous updates since then as information about the virus and vaccines has evolved. 

“We know a lot more about COVID-19 and the vaccines now, and we can use that knowledge to minimize the confusion and enhance the protection we can offer to our immunocompromised patients,” said advisory committee co-leader Lindsey Baden, MD, an infectious diseases specialist at the Dana-Farber Cancer Institute, Boston.

The latest iteration of the NCCN’s COVID guidelines includes an update for patients who initially received Johnson & Johnson’s single-shot vaccine, including a recommendation that patients receive an mRNA vaccine for both the first and second booster.

The group also updated dosing recommendations for pre-exposure prevention with tixagevimab plus cilgavimab (Evusheld, AstraZeneca), suggesting 300 mg of each monoclonal antibody instead of 150 mg, based on in vitro activity against Omicron variants.

The group noted that the Moderna and Pfizer shots can be used interchangeably for boosters.

“The NCCN Committee considers both homologous and heterologous boosters to be appropriate options,” the experts wrote.

A version of this article first appeared on Medscape.com.

Two new cancer drugs have been recommended for approval in the European Union (EU): capmatinib (Tabrecta, Novartis) for the treatment of advanced non–small cell lung cancer (NSCLC) with certain mutations, and conditional approval of mosunetuzumab (Lunsumio, Roche) for relapsed or refractory follicular lymphoma.

The European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion for the two products at its April meeting.
 

New drug for certain lung cancer patients

Capmatinib is a selective, reversible inhibitor of MET tyrosine kinase and is indicated for the treatment of patients with advanced NSCLC harboring alterations leading to mesenchymal-epithelial transition factor gene exon 14 (METex14) skipping. Patients must have already been treated with immunotherapy and/or platinum-based chemotherapy.

The product is approved in the United States, and the Food and Drug Administration noted that it is the first approved treatment for NSCLC with MET exon 14-skipping mutations.

The FDA granted the drug an accelerated approval based on overall response rate and response duration in the GEOMETRY mono-1 trial, which included a cohort of previously treated and treatment-naive patients. The overall response rate was 68% in the treatment-naive patients and 41% in the previously treated patients. The median duration of response was 12.6 months and 9.7 months.

The most common side effects were peripheral edema, nausea, fatigue, vomiting, dyspnea, and decreased appetite.
 

Conditional approval for lymphoma

Mosunetuzumab is an investigational bispecific antibody targeting CD20 and CD3, and redirects T cells to engage and eliminate malignant B cells.

The CHMP recommended a conditional approval for this drug for use as monotherapy for the treatment of adult patients with relapsed or refractory follicular lymphoma  who have received at least two prior systemic therapies.

Mosunetuzumab was reviewed under EMA’s accelerated access program, which usually takes 150 evaluation days as opposed to 210, and it was designated as an orphan medicine during its development.

The EMA stated that the benefits of this product are the high proportion of patients with a complete response and the durability of the treatment response.

As previously reported by this news organization, results from a phase 2 expansion study showed that when used as monotherapy, it induced high response rates and long-duration responses in patients with heavily pretreated, relapsed, or refractory follicular lymphoma.

At a median follow-up of 18.3 months, 54 of 90 patients (60%) had a complete response, and 18 (20%) had a partial response after treatment with mosunetuzumab.

The most common reported side effects were cytokine release syndrome, neutropenia, pyrexia (fever), hypophosphatemia, and headache.

Mosunetuzumab is awaiting FDA approval in the United States.

A conditional marketing authorization from CHMP is granted to products that meet an unmet medical need, and when the benefit to public health of immediate availability outweighs the risk inherent in the fact that additional data are still required. The marketing authorization holder is expected to provide comprehensive clinical data at a later stage.

Detailed recommendations for the use of both products will be described in the summary of product characteristics (SmPC), which will be published in the European public assessment report (EPAR) and made available in all official European Union languages after the marketing authorization has been granted by the European Commission.

A version of this article first appeared on Medscape.com.

Two new cancer drugs have been recommended for approval in the European Union (EU): capmatinib (Tabrecta, Novartis) for the treatment of advanced non–small cell lung cancer (NSCLC) with certain mutations, and conditional approval of mosunetuzumab (Lunsumio, Roche) for relapsed or refractory follicular lymphoma.

The European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion for the two products at its April meeting.
 

New drug for certain lung cancer patients

Capmatinib is a selective, reversible inhibitor of MET tyrosine kinase and is indicated for the treatment of patients with advanced NSCLC harboring alterations leading to mesenchymal-epithelial transition factor gene exon 14 (METex14) skipping. Patients must have already been treated with immunotherapy and/or platinum-based chemotherapy.

The product is approved in the United States, and the Food and Drug Administration noted that it is the first approved treatment for NSCLC with MET exon 14-skipping mutations.

The FDA granted the drug an accelerated approval based on overall response rate and response duration in the GEOMETRY mono-1 trial, which included a cohort of previously treated and treatment-naive patients. The overall response rate was 68% in the treatment-naive patients and 41% in the previously treated patients. The median duration of response was 12.6 months and 9.7 months.

The most common side effects were peripheral edema, nausea, fatigue, vomiting, dyspnea, and decreased appetite.
 

Conditional approval for lymphoma

Mosunetuzumab is an investigational bispecific antibody targeting CD20 and CD3, and redirects T cells to engage and eliminate malignant B cells.

The CHMP recommended a conditional approval for this drug for use as monotherapy for the treatment of adult patients with relapsed or refractory follicular lymphoma  who have received at least two prior systemic therapies.

Mosunetuzumab was reviewed under EMA’s accelerated access program, which usually takes 150 evaluation days as opposed to 210, and it was designated as an orphan medicine during its development.

The EMA stated that the benefits of this product are the high proportion of patients with a complete response and the durability of the treatment response.

As previously reported by this news organization, results from a phase 2 expansion study showed that when used as monotherapy, it induced high response rates and long-duration responses in patients with heavily pretreated, relapsed, or refractory follicular lymphoma.

At a median follow-up of 18.3 months, 54 of 90 patients (60%) had a complete response, and 18 (20%) had a partial response after treatment with mosunetuzumab.

The most common reported side effects were cytokine release syndrome, neutropenia, pyrexia (fever), hypophosphatemia, and headache.

Mosunetuzumab is awaiting FDA approval in the United States.

A conditional marketing authorization from CHMP is granted to products that meet an unmet medical need, and when the benefit to public health of immediate availability outweighs the risk inherent in the fact that additional data are still required. The marketing authorization holder is expected to provide comprehensive clinical data at a later stage.

Detailed recommendations for the use of both products will be described in the summary of product characteristics (SmPC), which will be published in the European public assessment report (EPAR) and made available in all official European Union languages after the marketing authorization has been granted by the European Commission.

A version of this article first appeared on Medscape.com.

Two new cancer drugs have been recommended for approval in the European Union (EU): capmatinib (Tabrecta, Novartis) for the treatment of advanced non–small cell lung cancer (NSCLC) with certain mutations, and conditional approval of mosunetuzumab (Lunsumio, Roche) for relapsed or refractory follicular lymphoma.

The European Medicines Agency (EMA) Committee for Medicinal Products for Human Use (CHMP) issued a positive opinion for the two products at its April meeting.
 

New drug for certain lung cancer patients

Capmatinib is a selective, reversible inhibitor of MET tyrosine kinase and is indicated for the treatment of patients with advanced NSCLC harboring alterations leading to mesenchymal-epithelial transition factor gene exon 14 (METex14) skipping. Patients must have already been treated with immunotherapy and/or platinum-based chemotherapy.

The product is approved in the United States, and the Food and Drug Administration noted that it is the first approved treatment for NSCLC with MET exon 14-skipping mutations.

The FDA granted the drug an accelerated approval based on overall response rate and response duration in the GEOMETRY mono-1 trial, which included a cohort of previously treated and treatment-naive patients. The overall response rate was 68% in the treatment-naive patients and 41% in the previously treated patients. The median duration of response was 12.6 months and 9.7 months.

The most common side effects were peripheral edema, nausea, fatigue, vomiting, dyspnea, and decreased appetite.
 

Conditional approval for lymphoma

Mosunetuzumab is an investigational bispecific antibody targeting CD20 and CD3, and redirects T cells to engage and eliminate malignant B cells.

The CHMP recommended a conditional approval for this drug for use as monotherapy for the treatment of adult patients with relapsed or refractory follicular lymphoma  who have received at least two prior systemic therapies.

Mosunetuzumab was reviewed under EMA’s accelerated access program, which usually takes 150 evaluation days as opposed to 210, and it was designated as an orphan medicine during its development.

The EMA stated that the benefits of this product are the high proportion of patients with a complete response and the durability of the treatment response.

As previously reported by this news organization, results from a phase 2 expansion study showed that when used as monotherapy, it induced high response rates and long-duration responses in patients with heavily pretreated, relapsed, or refractory follicular lymphoma.

At a median follow-up of 18.3 months, 54 of 90 patients (60%) had a complete response, and 18 (20%) had a partial response after treatment with mosunetuzumab.

The most common reported side effects were cytokine release syndrome, neutropenia, pyrexia (fever), hypophosphatemia, and headache.

Mosunetuzumab is awaiting FDA approval in the United States.

A conditional marketing authorization from CHMP is granted to products that meet an unmet medical need, and when the benefit to public health of immediate availability outweighs the risk inherent in the fact that additional data are still required. The marketing authorization holder is expected to provide comprehensive clinical data at a later stage.

Detailed recommendations for the use of both products will be described in the summary of product characteristics (SmPC), which will be published in the European public assessment report (EPAR) and made available in all official European Union languages after the marketing authorization has been granted by the European Commission.

A version of this article first appeared on Medscape.com.

Key clinical point: High circulating D-dimer levels are a risk factor for mortality and venous thromboembolism (VTE) events in patients with lung cancer.

Major finding: The meta-analysis showed that high vs. low circulating D-dimer levels were associated with a higher risk for lung cancer mortality (hazard ratio [HR] 1.62; 95% CI 1.39-1.88). Additionally, the external validation cohort demonstrated that elevated D-dimer levels were associated with a higher risk for overall mortality (HR 1.39; 95% CI 1.13-1.72) and VTE events (HR 3.98; P = .002).

Study details: The data come from a meta-analysis of 19 cohort studies (n = 5819) and an external validation cohort (n = 540).

Disclosures: The study was funded by the Social Development Project of Jiangsu Province, China, and the Project of Hygiene and Health Committee of Jiangsu Province, China. The authors declared no conflicts of interest.

Source: Li J et al. Circulating D-dimers increase the risk of mortality and venous thromboembolism in patients with lung cancer: A systematic analysis combined with external validation. Front Med (Lausanne). 2022;9:853941 (Mar 2). Doi: 10.3389/fmed.2022.853941

Key clinical point: High circulating D-dimer levels are a risk factor for mortality and venous thromboembolism (VTE) events in patients with lung cancer.

Major finding: The meta-analysis showed that high vs. low circulating D-dimer levels were associated with a higher risk for lung cancer mortality (hazard ratio [HR] 1.62; 95% CI 1.39-1.88). Additionally, the external validation cohort demonstrated that elevated D-dimer levels were associated with a higher risk for overall mortality (HR 1.39; 95% CI 1.13-1.72) and VTE events (HR 3.98; P = .002).

Study details: The data come from a meta-analysis of 19 cohort studies (n = 5819) and an external validation cohort (n = 540).

Disclosures: The study was funded by the Social Development Project of Jiangsu Province, China, and the Project of Hygiene and Health Committee of Jiangsu Province, China. The authors declared no conflicts of interest.

Source: Li J et al. Circulating D-dimers increase the risk of mortality and venous thromboembolism in patients with lung cancer: A systematic analysis combined with external validation. Front Med (Lausanne). 2022;9:853941 (Mar 2). Doi: 10.3389/fmed.2022.853941

Key clinical point: High circulating D-dimer levels are a risk factor for mortality and venous thromboembolism (VTE) events in patients with lung cancer.

Major finding: The meta-analysis showed that high vs. low circulating D-dimer levels were associated with a higher risk for lung cancer mortality (hazard ratio [HR] 1.62; 95% CI 1.39-1.88). Additionally, the external validation cohort demonstrated that elevated D-dimer levels were associated with a higher risk for overall mortality (HR 1.39; 95% CI 1.13-1.72) and VTE events (HR 3.98; P = .002).

Study details: The data come from a meta-analysis of 19 cohort studies (n = 5819) and an external validation cohort (n = 540).

Disclosures: The study was funded by the Social Development Project of Jiangsu Province, China, and the Project of Hygiene and Health Committee of Jiangsu Province, China. The authors declared no conflicts of interest.

Source: Li J et al. Circulating D-dimers increase the risk of mortality and venous thromboembolism in patients with lung cancer: A systematic analysis combined with external validation. Front Med (Lausanne). 2022;9:853941 (Mar 2). Doi: 10.3389/fmed.2022.853941

Key clinical point: Addition of an antiangiogenic drug to second-line therapy may boost overall survival (OS) and progression-free survival (PFS) in patients with advanced non–small-cell lung cancer (NSCLC).

Major finding: The antiangiogenic drug plus second-line therapy vs. second-line therapy alone improved OS by 7% (hazard ratio [HR] 0.93; P = .005) and PFS by 20% (HR 0.80; P < .0001). The antiangiogenic group had a greater frequency of grade ≥3 toxicity.

Study details: The findings come from a patient data meta-analysis of 16 randomized controlled trials including 8629 participants.

Disclosures: The study did not receive any external funding. R Herbst, M Reck, EB Garon, GV Scagliotti, R Ramlau, N Hanna, J Vansteenkiste, K Yoh, HJM Groen, JV Heymach, and RS Heist were authors for some of the individual trials included in the meta-analysis. The other authors declared no conflicts of interest.

Source: Remon J et al. ANtiangiogenic Second-line Lung cancer Meta-Analysis on individual patient data in non-small cell lung cancer: ANSELMA. Eur J Cancer. 2022;166:112-125 (Mar 11). Doi:  10.1016/j.ejca.2022.02.002

Key clinical point: Addition of an antiangiogenic drug to second-line therapy may boost overall survival (OS) and progression-free survival (PFS) in patients with advanced non–small-cell lung cancer (NSCLC).

Major finding: The antiangiogenic drug plus second-line therapy vs. second-line therapy alone improved OS by 7% (hazard ratio [HR] 0.93; P = .005) and PFS by 20% (HR 0.80; P < .0001). The antiangiogenic group had a greater frequency of grade ≥3 toxicity.

Study details: The findings come from a patient data meta-analysis of 16 randomized controlled trials including 8629 participants.

Disclosures: The study did not receive any external funding. R Herbst, M Reck, EB Garon, GV Scagliotti, R Ramlau, N Hanna, J Vansteenkiste, K Yoh, HJM Groen, JV Heymach, and RS Heist were authors for some of the individual trials included in the meta-analysis. The other authors declared no conflicts of interest.

Source: Remon J et al. ANtiangiogenic Second-line Lung cancer Meta-Analysis on individual patient data in non-small cell lung cancer: ANSELMA. Eur J Cancer. 2022;166:112-125 (Mar 11). Doi:  10.1016/j.ejca.2022.02.002

Key clinical point: Addition of an antiangiogenic drug to second-line therapy may boost overall survival (OS) and progression-free survival (PFS) in patients with advanced non–small-cell lung cancer (NSCLC).

Major finding: The antiangiogenic drug plus second-line therapy vs. second-line therapy alone improved OS by 7% (hazard ratio [HR] 0.93; P = .005) and PFS by 20% (HR 0.80; P < .0001). The antiangiogenic group had a greater frequency of grade ≥3 toxicity.

Study details: The findings come from a patient data meta-analysis of 16 randomized controlled trials including 8629 participants.

Disclosures: The study did not receive any external funding. R Herbst, M Reck, EB Garon, GV Scagliotti, R Ramlau, N Hanna, J Vansteenkiste, K Yoh, HJM Groen, JV Heymach, and RS Heist were authors for some of the individual trials included in the meta-analysis. The other authors declared no conflicts of interest.

Source: Remon J et al. ANtiangiogenic Second-line Lung cancer Meta-Analysis on individual patient data in non-small cell lung cancer: ANSELMA. Eur J Cancer. 2022;166:112-125 (Mar 11). Doi:  10.1016/j.ejca.2022.02.002

Key clinical point: Patients with advanced nonsquamous non–small-cell lung cancer (NSCLC) receiving first-line immune checkpoint inhibitors plus chemotherapy (ICI-chemo) have better overall survival (OS) than those receiving first-line bevacizumab plus chemotherapy (bev-chemo).

Major finding: Patients who received first-line ICI-chemo had a 21% longer OS than those who received bev-chemo (hazard ratio 0.79; 95% CI 0.66-0.94). There were no differences between the 2 groups in progression-free survival, objective response rate, and grade ≥3 treatment-related adverse events.

Study details: The data come from a network meta-analysis of 15 randomized controlled trials including 6561 patients with advanced nonsquamous NSCLC.

Disclosures: No funding information was available. The authors declared no conflicts of interest.

Source: Zhai J et al. First-line PD-1/PD-L1 inhibitors plus chemotherapy versus bevacizumab plus chemotherapy for advanced non-squamous non-small cell lung cancer: A Bayesian network meta-analysis of randomized controlled trials. Cancer Med. 2022 (Mar 22). Doi: 10.1002/cam4.4589

Key clinical point: Patients with advanced nonsquamous non–small-cell lung cancer (NSCLC) receiving first-line immune checkpoint inhibitors plus chemotherapy (ICI-chemo) have better overall survival (OS) than those receiving first-line bevacizumab plus chemotherapy (bev-chemo).

Major finding: Patients who received first-line ICI-chemo had a 21% longer OS than those who received bev-chemo (hazard ratio 0.79; 95% CI 0.66-0.94). There were no differences between the 2 groups in progression-free survival, objective response rate, and grade ≥3 treatment-related adverse events.

Study details: The data come from a network meta-analysis of 15 randomized controlled trials including 6561 patients with advanced nonsquamous NSCLC.

Disclosures: No funding information was available. The authors declared no conflicts of interest.

Source: Zhai J et al. First-line PD-1/PD-L1 inhibitors plus chemotherapy versus bevacizumab plus chemotherapy for advanced non-squamous non-small cell lung cancer: A Bayesian network meta-analysis of randomized controlled trials. Cancer Med. 2022 (Mar 22). Doi: 10.1002/cam4.4589

Key clinical point: Patients with advanced nonsquamous non–small-cell lung cancer (NSCLC) receiving first-line immune checkpoint inhibitors plus chemotherapy (ICI-chemo) have better overall survival (OS) than those receiving first-line bevacizumab plus chemotherapy (bev-chemo).

Major finding: Patients who received first-line ICI-chemo had a 21% longer OS than those who received bev-chemo (hazard ratio 0.79; 95% CI 0.66-0.94). There were no differences between the 2 groups in progression-free survival, objective response rate, and grade ≥3 treatment-related adverse events.

Study details: The data come from a network meta-analysis of 15 randomized controlled trials including 6561 patients with advanced nonsquamous NSCLC.

Disclosures: No funding information was available. The authors declared no conflicts of interest.

Source: Zhai J et al. First-line PD-1/PD-L1 inhibitors plus chemotherapy versus bevacizumab plus chemotherapy for advanced non-squamous non-small cell lung cancer: A Bayesian network meta-analysis of randomized controlled trials. Cancer Med. 2022 (Mar 22). Doi: 10.1002/cam4.4589

Key clinical point: Platinum-doublet chemotherapy as the second-line treatment may offer an overall survival (OS) advantage over cytotoxic chemotherapy without platinum in relapsed patients with unresectable stage III non–small-cell lung cancer (NSCLC).

Major finding: The platinum group had a longer survival than the nonplatinum group (median OS 21.5 vs. 10.5 months; hazard ratio [HR] 0.54; P < .001). The platinum group also had longer survival than the nonplatinum group, when assessed from the beginning of chemoradiotherapy (median OS 34.9 vs. 21.8 months; HR 0.58; P = .001).

Study details: The data come from a retrospective cohort study that included 320 patients with unresectable stage III NSCLC from a Japanese lung cancer registry.

Disclosures: The study was funded by the Japan Society for Respiratory Endoscopy, Japanese Association for Thoracic Surgery, Japanese Association for Chest Surgery, Japanese Respiratory Society, and Japan Lung Cancer Society. E Miyawaki, K Takahashi, E Miyaoka, I Yoshino, and H Date did not report any disclosures. The other authors reported ties with one or more pharmaceutical companies.

Source: Miyawaki E et al. Efficacy of platinum agents for stage III non–small-cell lung cancer following platinum-based chemoradiotherapy: a retrospective study. BMC Cancer. 2022;22:342 (Mar 29). Doi: 10.1186/s12885-022-09441-3

Key clinical point: Platinum-doublet chemotherapy as the second-line treatment may offer an overall survival (OS) advantage over cytotoxic chemotherapy without platinum in relapsed patients with unresectable stage III non–small-cell lung cancer (NSCLC).

Major finding: The platinum group had a longer survival than the nonplatinum group (median OS 21.5 vs. 10.5 months; hazard ratio [HR] 0.54; P < .001). The platinum group also had longer survival than the nonplatinum group, when assessed from the beginning of chemoradiotherapy (median OS 34.9 vs. 21.8 months; HR 0.58; P = .001).

Study details: The data come from a retrospective cohort study that included 320 patients with unresectable stage III NSCLC from a Japanese lung cancer registry.

Disclosures: The study was funded by the Japan Society for Respiratory Endoscopy, Japanese Association for Thoracic Surgery, Japanese Association for Chest Surgery, Japanese Respiratory Society, and Japan Lung Cancer Society. E Miyawaki, K Takahashi, E Miyaoka, I Yoshino, and H Date did not report any disclosures. The other authors reported ties with one or more pharmaceutical companies.

Source: Miyawaki E et al. Efficacy of platinum agents for stage III non–small-cell lung cancer following platinum-based chemoradiotherapy: a retrospective study. BMC Cancer. 2022;22:342 (Mar 29). Doi: 10.1186/s12885-022-09441-3

Key clinical point: Platinum-doublet chemotherapy as the second-line treatment may offer an overall survival (OS) advantage over cytotoxic chemotherapy without platinum in relapsed patients with unresectable stage III non–small-cell lung cancer (NSCLC).

Major finding: The platinum group had a longer survival than the nonplatinum group (median OS 21.5 vs. 10.5 months; hazard ratio [HR] 0.54; P < .001). The platinum group also had longer survival than the nonplatinum group, when assessed from the beginning of chemoradiotherapy (median OS 34.9 vs. 21.8 months; HR 0.58; P = .001).

Study details: The data come from a retrospective cohort study that included 320 patients with unresectable stage III NSCLC from a Japanese lung cancer registry.

Disclosures: The study was funded by the Japan Society for Respiratory Endoscopy, Japanese Association for Thoracic Surgery, Japanese Association for Chest Surgery, Japanese Respiratory Society, and Japan Lung Cancer Society. E Miyawaki, K Takahashi, E Miyaoka, I Yoshino, and H Date did not report any disclosures. The other authors reported ties with one or more pharmaceutical companies.

Source: Miyawaki E et al. Efficacy of platinum agents for stage III non–small-cell lung cancer following platinum-based chemoradiotherapy: a retrospective study. BMC Cancer. 2022;22:342 (Mar 29). Doi: 10.1186/s12885-022-09441-3

Key clinical point: A Japanese real-world study found no overall survival (OS) benefit with adjuvant tegafur-uracil (UFT) chemotherapy compared with no chemotherapy in patients with completely resected stage I non–small-cell lung cancer (NSCLC).

Major finding: There was no significant difference in OS between the UFT and no chemotherapy groups (multivariate analysis: P = .3285; univariate analysis: P = .7554), with the exception of a subgroup with a tumor size of >3 cm and without ground-glass attenuation who benefitted from UFT (univariate analysis: hazard ratio 0.71; log-rank P = .0414).

Study details: In a real-world observational cohort study, patients treated with adjuvant UFT (n = 1549) were compared with those treated without any adjuvant chemotherapy (n = 3338).

Disclosures: The study was funded by Taiho Pharmaceutical. The authors reported ties with one or more pharmaceutical companies, including Taiho.

Source: Shukuya T et al. Efficacy of adjuvant chemotherapy with tegafur/uracil in patients with completely resected, node-negative non-small cell lung cancer – real-world data in the era of molecularly targeted agents and immunotherapy. JTO Clin Res Rep. 2022 (Apr 6). Doi:  10.1016/j.jtocrr.2022.100320

Key clinical point: A Japanese real-world study found no overall survival (OS) benefit with adjuvant tegafur-uracil (UFT) chemotherapy compared with no chemotherapy in patients with completely resected stage I non–small-cell lung cancer (NSCLC).

Major finding: There was no significant difference in OS between the UFT and no chemotherapy groups (multivariate analysis: P = .3285; univariate analysis: P = .7554), with the exception of a subgroup with a tumor size of >3 cm and without ground-glass attenuation who benefitted from UFT (univariate analysis: hazard ratio 0.71; log-rank P = .0414).

Study details: In a real-world observational cohort study, patients treated with adjuvant UFT (n = 1549) were compared with those treated without any adjuvant chemotherapy (n = 3338).

Disclosures: The study was funded by Taiho Pharmaceutical. The authors reported ties with one or more pharmaceutical companies, including Taiho.

Source: Shukuya T et al. Efficacy of adjuvant chemotherapy with tegafur/uracil in patients with completely resected, node-negative non-small cell lung cancer – real-world data in the era of molecularly targeted agents and immunotherapy. JTO Clin Res Rep. 2022 (Apr 6). Doi:  10.1016/j.jtocrr.2022.100320

Key clinical point: A Japanese real-world study found no overall survival (OS) benefit with adjuvant tegafur-uracil (UFT) chemotherapy compared with no chemotherapy in patients with completely resected stage I non–small-cell lung cancer (NSCLC).

Major finding: There was no significant difference in OS between the UFT and no chemotherapy groups (multivariate analysis: P = .3285; univariate analysis: P = .7554), with the exception of a subgroup with a tumor size of >3 cm and without ground-glass attenuation who benefitted from UFT (univariate analysis: hazard ratio 0.71; log-rank P = .0414).

Study details: In a real-world observational cohort study, patients treated with adjuvant UFT (n = 1549) were compared with those treated without any adjuvant chemotherapy (n = 3338).

Disclosures: The study was funded by Taiho Pharmaceutical. The authors reported ties with one or more pharmaceutical companies, including Taiho.

Source: Shukuya T et al. Efficacy of adjuvant chemotherapy with tegafur/uracil in patients with completely resected, node-negative non-small cell lung cancer – real-world data in the era of molecularly targeted agents and immunotherapy. JTO Clin Res Rep. 2022 (Apr 6). Doi:  10.1016/j.jtocrr.2022.100320

Key clinical point: Patients with lung cancer have a high prevalence of frailty, which significantly increases the risk for mortality compared with nonfrail patients with lung cancer.

Major finding: The prevalence of frailty in patients with lung cancer was 45% (95% CI 28%-61%). Frailty vs. no frailty in patients with lung cancer was associated with a 3-fold higher mortality risk (hazard ratio 3.02; P < .001).

Study details: The data come from a meta-analysis of 16 studies including 4183 patients with lung cancer (mean age 65-80.75 years).

Disclosures: The study received no funding. L Bencivenga reported receiving research grants from multiple organizations. The other authors reported no conflicts of interest.

Source: Komici K et al. Frailty in patients with lung cancer: A systematic review and meta-analysis. Chest. 2022 (Feb 22). Doi: 10.1016/j.chest.2022.02.027

Key clinical point: Patients with lung cancer have a high prevalence of frailty, which significantly increases the risk for mortality compared with nonfrail patients with lung cancer.

Major finding: The prevalence of frailty in patients with lung cancer was 45% (95% CI 28%-61%). Frailty vs. no frailty in patients with lung cancer was associated with a 3-fold higher mortality risk (hazard ratio 3.02; P < .001).

Study details: The data come from a meta-analysis of 16 studies including 4183 patients with lung cancer (mean age 65-80.75 years).

Disclosures: The study received no funding. L Bencivenga reported receiving research grants from multiple organizations. The other authors reported no conflicts of interest.

Source: Komici K et al. Frailty in patients with lung cancer: A systematic review and meta-analysis. Chest. 2022 (Feb 22). Doi: 10.1016/j.chest.2022.02.027

Key clinical point: Patients with lung cancer have a high prevalence of frailty, which significantly increases the risk for mortality compared with nonfrail patients with lung cancer.

Major finding: The prevalence of frailty in patients with lung cancer was 45% (95% CI 28%-61%). Frailty vs. no frailty in patients with lung cancer was associated with a 3-fold higher mortality risk (hazard ratio 3.02; P < .001).

Study details: The data come from a meta-analysis of 16 studies including 4183 patients with lung cancer (mean age 65-80.75 years).

Disclosures: The study received no funding. L Bencivenga reported receiving research grants from multiple organizations. The other authors reported no conflicts of interest.

Source: Komici K et al. Frailty in patients with lung cancer: A systematic review and meta-analysis. Chest. 2022 (Feb 22). Doi: 10.1016/j.chest.2022.02.027

Key clinical point: Adjuvant pembrolizumab boosts disease-free survival (DFS) in patients with early-stage non–small-cell lung cancer (NSCLC) after complete resection.

Major finding: DFS was 53.6 months in the pembrolizumab group vs. 42.0 months in the placebo group (hazard ratio 0.76; P = .0014). The DFS benefit was generally consistent across patients with programmed death ligand-1 tumor proportion score of <1%, 1%-49%, and ≥50%.

Study details: The data come from an interim analysis of the phase 3 PEARLS/KEYNOTE-091 trial, in which 1177 adults with stage IB, II, or IIIA NSCLC were randomly assigned to receive 200 mg pembrolizumab (n = 590) or placebo (n = 587) every 3 weeks.

Disclosures: The trial was funded by Merck Sharp & Dohme Corp. L Paz-Ares, MER O’Brien, U Dafni, K Oselin, D Isla, A Martinez-Marti, M Faehling, M Tsuboi, K Nakagawa, J Yang, SM Keller, RA Stahel, S Peters, and B Besse reported ties with one or more pharmaceutical companies, including Merck Sharp & Dohme. The other authors reported no conflicts of interest.

Source: Paz-Ares L et al. VP3-2022: Pembrolizumab (pembro) versus placebo for early-stage non-small cell lung cancer (NSCLC) following complete resection and adjuvant chemotherapy (chemo) when indicated: Randomized, triple-blind, phase III EORTC-1416-LCG/ETOP 8-15 – PEARLS/KEYNOTE-091 study. Ann Oncol. 2022;33(4):451-453 (Mar 17). Doi: 10.1016/j.annonc.2022.02.224

Key clinical point: Adjuvant pembrolizumab boosts disease-free survival (DFS) in patients with early-stage non–small-cell lung cancer (NSCLC) after complete resection.

Major finding: DFS was 53.6 months in the pembrolizumab group vs. 42.0 months in the placebo group (hazard ratio 0.76; P = .0014). The DFS benefit was generally consistent across patients with programmed death ligand-1 tumor proportion score of <1%, 1%-49%, and ≥50%.

Study details: The data come from an interim analysis of the phase 3 PEARLS/KEYNOTE-091 trial, in which 1177 adults with stage IB, II, or IIIA NSCLC were randomly assigned to receive 200 mg pembrolizumab (n = 590) or placebo (n = 587) every 3 weeks.

Disclosures: The trial was funded by Merck Sharp & Dohme Corp. L Paz-Ares, MER O’Brien, U Dafni, K Oselin, D Isla, A Martinez-Marti, M Faehling, M Tsuboi, K Nakagawa, J Yang, SM Keller, RA Stahel, S Peters, and B Besse reported ties with one or more pharmaceutical companies, including Merck Sharp & Dohme. The other authors reported no conflicts of interest.

Source: Paz-Ares L et al. VP3-2022: Pembrolizumab (pembro) versus placebo for early-stage non-small cell lung cancer (NSCLC) following complete resection and adjuvant chemotherapy (chemo) when indicated: Randomized, triple-blind, phase III EORTC-1416-LCG/ETOP 8-15 – PEARLS/KEYNOTE-091 study. Ann Oncol. 2022;33(4):451-453 (Mar 17). Doi: 10.1016/j.annonc.2022.02.224

Key clinical point: Adjuvant pembrolizumab boosts disease-free survival (DFS) in patients with early-stage non–small-cell lung cancer (NSCLC) after complete resection.

Major finding: DFS was 53.6 months in the pembrolizumab group vs. 42.0 months in the placebo group (hazard ratio 0.76; P = .0014). The DFS benefit was generally consistent across patients with programmed death ligand-1 tumor proportion score of <1%, 1%-49%, and ≥50%.

Study details: The data come from an interim analysis of the phase 3 PEARLS/KEYNOTE-091 trial, in which 1177 adults with stage IB, II, or IIIA NSCLC were randomly assigned to receive 200 mg pembrolizumab (n = 590) or placebo (n = 587) every 3 weeks.

Disclosures: The trial was funded by Merck Sharp & Dohme Corp. L Paz-Ares, MER O’Brien, U Dafni, K Oselin, D Isla, A Martinez-Marti, M Faehling, M Tsuboi, K Nakagawa, J Yang, SM Keller, RA Stahel, S Peters, and B Besse reported ties with one or more pharmaceutical companies, including Merck Sharp & Dohme. The other authors reported no conflicts of interest.

Source: Paz-Ares L et al. VP3-2022: Pembrolizumab (pembro) versus placebo for early-stage non-small cell lung cancer (NSCLC) following complete resection and adjuvant chemotherapy (chemo) when indicated: Randomized, triple-blind, phase III EORTC-1416-LCG/ETOP 8-15 – PEARLS/KEYNOTE-091 study. Ann Oncol. 2022;33(4):451-453 (Mar 17). Doi: 10.1016/j.annonc.2022.02.224