Desai, Aakash P

Importance Although cancer-related mortality continues to decline, lung cancer remains the No. 1 cause of cancer deaths in the US. Almost half of the patients with non–small cell lung cancer (NSCLC) are diagnosed with early-stage, local or regional disease and are at high risk of recurrence within 5 years of diagnosis. Observations Immune checkpoint inhibitors (ICIs) have improved outcomes for patients with metastatic NSCLC and have recently been tested in multiple clinical trials to determine their efficacy in the neoadjuvant or adjuvant setting for patients with local or regional disease. The landscape for perioperative ICIs in lung cancer is evolving rapidly, with recently reported and soon to mature clinical trials; however, the recent data highlight the potential of ICIs to increase response rates and decrease rates of relapse in early stages of lung cancer. Concurrently, novel applications of cell-free DNA may guide perioperative management strategies. Conclusions and Relevance This article reviews the various approaches of incorporating perioperative use of immunotherapeutic agents for the treatment of early stages of NSCLC.

Abstract An antibody-drug conjugate (ADC) comprises a monoclonal antibody that is specific to a tumor cell protein, bound to a cytotoxic agent, known as the payload. The use of ADCs is already common practice in several cancers, thanks to their efficacy and potentially more manageable toxicity profile, resulting from the release of the cytostatic payload directly in the tumors. Currently, early-phase trials of ADCs in non–small cell lung cancer are rapidly gaining ground, with promising results targeting HER2 (human epidermal growth factor 2), HER3, TROP2 (trophoblast cell surface antigen 2), MET, CEACAM5 (carcinoembryonic antigen–related cell adhesion molecule 5), and PTK7 (tyrosine protein kinase–like 7). Unfortunately, in small cell lung cancer, trials targeting the ubiquitous DLL3 (delta-like ligand 3) protein have failed to show clinically relevant results, despite significant toxicity.

ImportanceCytokine storm due to COVID-19 can cause high morbidity and mortality and may be more common in patients with cancer treated with immunotherapy (IO) due to immune system activation.ObjectiveTo determine the association of baseline immunosuppression and/or IO-based therapies with COVID-19 severity and cytokine storm in patients with cancer.Design, Setting, and ParticipantsThis registry-based retrospective cohort study included 12 046 patients reported to the COVID-19 and Cancer Consortium (CCC19) registry from March 2020 to May 2022. The CCC19 registry is a centralized international multi-institutional registry of patients with COVID-19 with a current or past diagnosis of cancer. Records analyzed included patients with active or previous cancer who had a laboratory-confirmed infection with SARS-CoV-2 by polymerase chain reaction and/or serologic findings.ExposuresImmunosuppression due to therapy; systemic anticancer therapy (IO or non-IO).Main Outcomes and MeasuresThe primary outcome was a 5-level ordinal scale of COVID-19 severity: no complications; hospitalized without requiring oxygen; hospitalized and required oxygen; intensive care unit admission and/or mechanical ventilation; death. The secondary outcome was the occurrence of cytokine storm.ResultsThe median age of the entire cohort was 65 years (interquartile range [IQR], 54-74) years and 6359 patients were female (52.8%) and 6598 (54.8%) were non-Hispanic White. A total of 599 (5.0%) patients received IO, whereas 4327 (35.9%) received non-IO systemic anticancer therapies, and 7120 (59.1%) did not receive any antineoplastic regimen within 3 months prior to COVID-19 diagnosis. Although no difference in COVID-19 severity and cytokine storm was found in the IO group compared with the untreated group in the total cohort (adjusted odds ratio [aOR], 0.80; 95% CI, 0.56-1.13, and aOR, 0.89; 95% CI, 0.41-1.93, respectively), patients with baseline immunosuppression treated with IO (vs untreated) had worse COVID-19 severity and cytokine storm (aOR, 3.33; 95% CI, 1.38-8.01, and aOR, 4.41; 95% CI, 1.71-11.38, respectively). Patients with immunosuppression receiving non-IO therapies (vs untreated) also had worse COVID-19 severity (aOR, 1.79; 95% CI, 1.36-2.35) and cytokine storm (aOR, 2.32; 95% CI, 1.42-3.79).Conclusions and RelevanceThis cohort study found that in patients with cancer and COVID-19, administration of systemic anticancer therapies, especially IO, in the context of baseline immunosuppression was associated with severe clinical outcomes and the development of cytokine storm.Trial RegistrationClinicalTrials.gov Identifier: NCT04354701

Lay summaryImmunotherapy has changed the landscape of cancer treatment. However, the benefit of immunotherapy is seen only in some cases, with most patients experiencing cancer progression despite treatment with immunotherapy. To overcome this, combination immunotherapy treatments are being studied. Herein, we propose for a precision‐driven approach for patient selection to identify successful combinations of immunotherapy to improve outcomes for patients with cancer.

The author of this essay uses his experience learning the complex planning and strategies of chess in childhood to illustrate the importance of informed strategy in the treatment of patients with cancer.

This JAMA Oncology Patient Page describes the use of systemic therapy in addition to surgery in the treatment of early-stage lung cancer.