Devika Das, MD, MSHQS, clinical assistant professor of hematology and oncology, University of Alabama at Birmingham (UAB) Medicine, discusses the use of neoadjuvant and adjuvant chemoimmunotherapy for patients with resectable non–small cell lung cancer (NSCLC), and emphasizes the importance of multidisciplinary collaboration when incorporating these regimens into treatment approaches.

It is vital that surgeons, specialists, and community oncologists all work collaboratively to determine the best treatment approach for patients with early-stage or advanced NSCLC, Das begins. This multidisciplinary approach is especially important because it may allow patients to receive neoadjuvant chemoimmunotherapy regimens, such as nivolumab (Opdivo) plus platinum-based chemotherapy, Das says. This 

regimen gained FDA approval in March 2022

 based on findings from the phase 3 CheckMate 816 trial (NCT02998528) in patients with stage IB to IIIA NSCLC.

In this trial, the neoadjuvant chemoimmunotherapy regimen produced a pathologic complete response rate of 24.0% vs 2.2% with chemotherapy alone across all patient subgroups, Das reports. Differences in PD-L1 expression, disease stage, and histology did not affect this outcome. Moreover, patients treated with neoadjuvant chemoimmunotherapy achieved a median event-free survival of 31.6 months vs 20.8 months with chemotherapy alone, she adds. Despite concerns regarding the effect of neoadjuvant chemoimmunotherapy on the difficulty of surgical resection and surgical outcomes, the agent was shown to be safe and effective, Das states. 

However, many patients with NSCLC will still undergo surgery before being referred to a medical oncology clinic in either the community or at academic centers, Das continues. For these patients who miss the window for neoadjuvant chemoimmunotherapy, the approval of adjuvant chemotherapy options is especially important, she states. Based on data from the phase 3 IMpower010 trial (NCT02486718) the 

FDA approved adjuvant atezolizumab (Tecentriq)

 following resection and platinum-based chemotherapy for patients with stage II to IIIA NSCLC expressing PD-L1 on 1% or more of tumor cells in October 2021. According to an interim analysis of overall survival (OS) data, adjuvant atezolizumab produced a 5-year OS rate of 76.8% vs 67.5% in the best supportive care arm for patients who had a PD-L1 expression of 1% or greater.

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Devika Das, MD, MSHQS, discusses the use of neoadjuvant and adjuvant chemoimmunotherapy for patients with resectable non–small cell lung cancer, and emphasizes the importance of multidisciplinary collaboration when incorporating these regimens into treatment approaches.

Dr Das on the Use of Neoadjuvant and Adjuvant Chemoimmunotherapy Regimens in NSCLC

Devika Das, MD, MSHQS, clinical assistant professor of hematology and oncology, University of Alabama at Birmingham (UAB) Medicine, discusses the activity and tolerability of lurbinectedin (Zepzelca) and topotecan as second-line regimens in extensive-stage small cell lung cancer (ES-SCLC).

Many patients with ES-SCLC will experience recurrence or relapse after initial treatment. However, the number of available and effective second-line options are unfortunatelylimited in this space, Das begins.

Prior to the FDA approval of lurbinectedin in 2020, the standard of care for relapsed ES-SCLC was the chemotherapy agent topotecan, Das explains. Across several randomized controlled clinical trials, the best response rate seen with this agent was 24.3% The median duration of response (DOR) is 18 weeks and median overall survival (OS) is 25 to 35 weeks. However, topotecan is associated with a high incidence of grade 3 or greater treatment-related adverse effects (AEs) in these trials.

The FDA granted accelerated approval to lurbinectedin for patients with metastatic SCLC who progressed on prior platinum-based chemotherapy based on findings from a single-arm, open-label, phase 2 basket trial (NCT02454972). In this trial of 105 patients, lurbinectedin produced an overall response rate of 35%, a median progression-free survival of 3.9 months, and a median OS of 9.3 months. Median DOR was 5.3 months with the agent. Regarding toxicities, 34.3% of patients had grade 3 or higher toxicities, and grade 1/2 toxicities were commonly observed.

A regimen’s AE profile has a substantial effect on a patient’s quality of life and greatly influences treatment selection, Das emphasizes. Although caution should be exercised when making cross-trial comparisons, lurbinectedin appears as effective and more tolerable than topotecan, Das says. Its activity in patients who are platinum-refractory also provides it with an advantage over topotecan, she adds.

Given the lack of research on potential alternatives to these agents, lurbinectedin isremains the best available option in the second line for patients who relapse within 6 months after previous treatment and cannot tolerate topotecan, Das states. An increased focus on the development of novel second-line therapeutics through clinical trials could address the continued need for more effective alternatives to lurbinectidin in relapsed ES-SCLC, Das concludes.

Devika Das, MD, MSHQS, discusses the activity and tolerability of lurbinectedin and topotecan as second-line regimens in extensive-stage small cell lung cancer.

Dr Das on the Limited Landscape of Second-line Treatment Options in ES-SCLC

Devika Das, MD, MSHQS, clinical assistant professor of hematology and oncology, University of Alabama at Birmingham (UAB) Medicine, discusses updated data on the use of immunotherapy and platinum-based chemotherapy regimens in extensive-stage small cell lung cancer (ES-SCLC).

Research into SCLC treatment fell short in the attempt to improve historicaloutcomes in ES-SCLC, Das begins. Despite attempts to modify standard treatment approaches in non–small cell lung cancer, carboplatin and etoposide combinations remained the standard of care (SOC) in this space for decades. However, the addition of immune checkpoint inhibitors to the treatment landscape has impacted frontline approaches.

FDA approved atezolizumab (Tecentriq) for the first-line treatment of ES-SCLC

 in combination with etoposide and either carboplatin or cisplatin based on data from the phase 3 IMpower-133 trial (NCT02763579), Das reports. In this trial, the atezolizumab regimen produced a 12-month overall survival (OS) rate of 51.7% (n =201) vs 38.2% with placebo (n =202).

Then, in 2020, first-line treatment with durvalumab (Imfinzi) plus platinum/etoposide gained FDA approval in this space, according to findings from the phase 3 CASPIAN trial (NCT03043872), Das adds. The 12-month OS rates were 52.8% in the durvalumab arm (n = 268) vs 39.3% in the platinum/etoposide arm (n = 269).

Updated survival data from the CASPIAN trial were reported in 2022, Das continues. The 3-year OS rate was 17.6% in patients who received the durvalumab regimen compared with 5.8% in patients who received platinum doublet chemotherapy, Das states. These results confirmed the use of durvalumab plus platinum/etoposide as a first-line SOC for ES-SCLC.

Despite these encouraging results, there are currently no biomarkers available to predict patient response and guide treatment selection in this population, creating an unmet need, Das notes. Ongoing clinical trials are attempting to address this deficit, she concludes. 

Devika Das, MD, MSHQS,discusses updated data on the use of immunotherapy and platinum-based chemotherapy regimens in extensive-stage small cell lung cancer.

Devika Das, MD, MSHQS

Articles

Dr Das on the Use of Neoadjuvant and Adjuvant Chemoimmunotherapy Regimens in NSCLC

Dr Das on the Limited Landscape of Second-line Treatment Options in ES-SCLC

Dr Das on Updated Data Supporting the Use of Chemoimmunotherapy Regimens in ES-SCLC