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In this edition of “How I will treat my next patient,” I take a look at two recent trials in non–small cell lung cancer (NSCLC). One summarizes a late analysis of a previously published randomized trial in stage IV NSCLC with three or fewer sites of metastasis – oligometastatic disease. The other reviews deidentified patient data to discern whether immune-targeted treatment might be valuable in particular subsets of NSCLC patients with EGFR mutations.
Local consolidative therapy
Daniel R. Gomez, MD, and colleagues published an updated analysis of progression-free survival (PFS) and an initial analysis of overall survival (OS) data in a randomized phase 2 trial in oligometastatic NSCLC. As originally published, patients were randomized to local consolidative treatment (LCT) versus standard maintenance therapy or observation (MT/O). Patients were required to have responding or stable disease after first-line systemic therapy prior to randomization.
Among the 49 patients who received LCT, there was a clear benefit of LCT (PFS of 14.2 months vs. 4.4 months for MT/O; P = .022; and median OS 41.2 months vs. 17.0 months; P = .017). The OS benefit was seen despite allowing crossover to LCT for patients who demonstrated disease progression in the MT/O arm.
What this means in practice
These data are exciting and move clinical research forward – if not, at this time, clinical practice. They support the ongoing clinical trials in NSCLC (NRG LU002) and breast cancer (NRG BR002) investigating the role of LCT in the oligometastatic setting.
For patients who are not candidates for (or choose not to participate in) these important phase 2R/3 trials, I believe that LCT should be discussed with all of the caveats that the authors appropriately mention, from the small number of patients because of the premature closure of the trial, to heterogeneous systemic regimens, to the lack of clarity on whether newer systemic therapies are better.
Immune checkpoint blockade
Historically, EGFR-mutated NSCLCs have not derived comparable benefit to EGFR-wild type (WT) tumors from checkpoint inhibitors. For that reason, in EGFR-mutated tumors, guidelines from the National Comprehensive Cancer Network (NCCN) suggest immune-targeted treatment should be used only on clinical trials or after receipt of EGFR-targeted tyrosine kinase inhibitors and cytotoxic chemotherapy. Several recent studies (IMpower and ATLANTIC), however, have suggested that selected EGFR-mutated patients can benefit from immune-targeted treatment.
Katherine Hastings, PhD, of Yale University, New Haven, Conn., and associates found, in a multi-institution clinical-molecular data review, that among the 44 of 171 EGFR-mutated tumors with L858R mutations, benefit from checkpoint inhibitors was comparable to WT tumors with regard to overall response rate and OS, but not PFS. Additionally, tumors with the EGFR T790M mutation demonstrated similar benefit from checkpoint inhibitors as in WT tumors, L858R-mutated tumors (but not exon 19 deleted tumors) had high tumor mutation burden, and PD-L1 expression did not influence outcome from immunotherapy.
What this means in practice
I agree with the modesty of the authors’ conclusion that these findings should not change clinical practice but rather should encourage further research into which patients with EGFR-mutant disease might benefit from immune-targeted therapy. For now, outside of a clinical trial, in EGFR-mutated patients, I will follow NCCN guidelines, using immune-targeted therapy off-study only with attentiveness to the particular immunotherapy regimens that have shown promise in the literature – and later, not earlier.
Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.
In this edition of “How I will treat my next patient,” I take a look at two recent trials in non–small cell lung cancer (NSCLC). One summarizes a late analysis of a previously published randomized trial in stage IV NSCLC with three or fewer sites of metastasis – oligometastatic disease. The other reviews deidentified patient data to discern whether immune-targeted treatment might be valuable in particular subsets of NSCLC patients with EGFR mutations.
Local consolidative therapy
Daniel R. Gomez, MD, and colleagues published an updated analysis of progression-free survival (PFS) and an initial analysis of overall survival (OS) data in a randomized phase 2 trial in oligometastatic NSCLC. As originally published, patients were randomized to local consolidative treatment (LCT) versus standard maintenance therapy or observation (MT/O). Patients were required to have responding or stable disease after first-line systemic therapy prior to randomization.
Among the 49 patients who received LCT, there was a clear benefit of LCT (PFS of 14.2 months vs. 4.4 months for MT/O; P = .022; and median OS 41.2 months vs. 17.0 months; P = .017). The OS benefit was seen despite allowing crossover to LCT for patients who demonstrated disease progression in the MT/O arm.
What this means in practice
These data are exciting and move clinical research forward – if not, at this time, clinical practice. They support the ongoing clinical trials in NSCLC (NRG LU002) and breast cancer (NRG BR002) investigating the role of LCT in the oligometastatic setting.
For patients who are not candidates for (or choose not to participate in) these important phase 2R/3 trials, I believe that LCT should be discussed with all of the caveats that the authors appropriately mention, from the small number of patients because of the premature closure of the trial, to heterogeneous systemic regimens, to the lack of clarity on whether newer systemic therapies are better.
Immune checkpoint blockade
Historically, EGFR-mutated NSCLCs have not derived comparable benefit to EGFR-wild type (WT) tumors from checkpoint inhibitors. For that reason, in EGFR-mutated tumors, guidelines from the National Comprehensive Cancer Network (NCCN) suggest immune-targeted treatment should be used only on clinical trials or after receipt of EGFR-targeted tyrosine kinase inhibitors and cytotoxic chemotherapy. Several recent studies (IMpower and ATLANTIC), however, have suggested that selected EGFR-mutated patients can benefit from immune-targeted treatment.
Katherine Hastings, PhD, of Yale University, New Haven, Conn., and associates found, in a multi-institution clinical-molecular data review, that among the 44 of 171 EGFR-mutated tumors with L858R mutations, benefit from checkpoint inhibitors was comparable to WT tumors with regard to overall response rate and OS, but not PFS. Additionally, tumors with the EGFR T790M mutation demonstrated similar benefit from checkpoint inhibitors as in WT tumors, L858R-mutated tumors (but not exon 19 deleted tumors) had high tumor mutation burden, and PD-L1 expression did not influence outcome from immunotherapy.
What this means in practice
I agree with the modesty of the authors’ conclusion that these findings should not change clinical practice but rather should encourage further research into which patients with EGFR-mutant disease might benefit from immune-targeted therapy. For now, outside of a clinical trial, in EGFR-mutated patients, I will follow NCCN guidelines, using immune-targeted therapy off-study only with attentiveness to the particular immunotherapy regimens that have shown promise in the literature – and later, not earlier.
Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.
In this edition of “How I will treat my next patient,” I take a look at two recent trials in non–small cell lung cancer (NSCLC). One summarizes a late analysis of a previously published randomized trial in stage IV NSCLC with three or fewer sites of metastasis – oligometastatic disease. The other reviews deidentified patient data to discern whether immune-targeted treatment might be valuable in particular subsets of NSCLC patients with EGFR mutations.
Local consolidative therapy
Daniel R. Gomez, MD, and colleagues published an updated analysis of progression-free survival (PFS) and an initial analysis of overall survival (OS) data in a randomized phase 2 trial in oligometastatic NSCLC. As originally published, patients were randomized to local consolidative treatment (LCT) versus standard maintenance therapy or observation (MT/O). Patients were required to have responding or stable disease after first-line systemic therapy prior to randomization.
Among the 49 patients who received LCT, there was a clear benefit of LCT (PFS of 14.2 months vs. 4.4 months for MT/O; P = .022; and median OS 41.2 months vs. 17.0 months; P = .017). The OS benefit was seen despite allowing crossover to LCT for patients who demonstrated disease progression in the MT/O arm.
What this means in practice
These data are exciting and move clinical research forward – if not, at this time, clinical practice. They support the ongoing clinical trials in NSCLC (NRG LU002) and breast cancer (NRG BR002) investigating the role of LCT in the oligometastatic setting.
For patients who are not candidates for (or choose not to participate in) these important phase 2R/3 trials, I believe that LCT should be discussed with all of the caveats that the authors appropriately mention, from the small number of patients because of the premature closure of the trial, to heterogeneous systemic regimens, to the lack of clarity on whether newer systemic therapies are better.
Immune checkpoint blockade
Historically, EGFR-mutated NSCLCs have not derived comparable benefit to EGFR-wild type (WT) tumors from checkpoint inhibitors. For that reason, in EGFR-mutated tumors, guidelines from the National Comprehensive Cancer Network (NCCN) suggest immune-targeted treatment should be used only on clinical trials or after receipt of EGFR-targeted tyrosine kinase inhibitors and cytotoxic chemotherapy. Several recent studies (IMpower and ATLANTIC), however, have suggested that selected EGFR-mutated patients can benefit from immune-targeted treatment.
Katherine Hastings, PhD, of Yale University, New Haven, Conn., and associates found, in a multi-institution clinical-molecular data review, that among the 44 of 171 EGFR-mutated tumors with L858R mutations, benefit from checkpoint inhibitors was comparable to WT tumors with regard to overall response rate and OS, but not PFS. Additionally, tumors with the EGFR T790M mutation demonstrated similar benefit from checkpoint inhibitors as in WT tumors, L858R-mutated tumors (but not exon 19 deleted tumors) had high tumor mutation burden, and PD-L1 expression did not influence outcome from immunotherapy.
What this means in practice
I agree with the modesty of the authors’ conclusion that these findings should not change clinical practice but rather should encourage further research into which patients with EGFR-mutant disease might benefit from immune-targeted therapy. For now, outside of a clinical trial, in EGFR-mutated patients, I will follow NCCN guidelines, using immune-targeted therapy off-study only with attentiveness to the particular immunotherapy regimens that have shown promise in the literature – and later, not earlier.
Dr. Lyss has been a community-based medical oncologist and clinical researcher for more than 35 years, practicing in St. Louis. His clinical and research interests are in the prevention, diagnosis, and treatment of breast and lung cancers and in expanding access to clinical trials to medically underserved populations.