Millie Das, MD, is a clinical professor of medicine – oncology in the Department of Medicine at Stanford University; a member of the Stanford Cancer Institute; and chief of Oncology at the VA Palo Alto Health Care System

Dr Das on Updates to the Standard First-Line Treatment Paradigm for ES-SCLC

“After many decades of trying novel therapies in combination with platinum and etoposide, [durvalumab] was the drug that led to [an] approval and led to a survival benefit in patients with this difficult-to-treat disease.”

Millie Das, MD, a clinical professor of medicine – oncology in the Department of Medicine at Stanford University; a member of the Stanford Cancer Institute; and chief of Oncology at the VA Palo Alto Health Care System, discussed standard-of-care treatment options for patients with previously untreated extensive-stage small cell lung cancer (ES-SCLC) and limited-stage SCLC (LS-SCLC).

For patients diagnosed with ES-SCLC, the current standard first-line treatment approach includes the addition of a PD-L1 inhibitor to the chemotherapy regimen of platinum plus etoposide, Das began. This strategy is supported by data from randomized phase 3 IMpower133 (NCT02763579) and CASPIAN (NCT03043872) studies. Based on these results, atezolizumab (Tecentriq) and durvalumab (Imfinzi), respectively, have received FDA approval for use in combination with chemotherapy in the initial treatment of patients with extensive-stage disease. This development represents a significant advancement in the management of SCLC, as prior attempts to improve outcomes by combining various investigational agents with platinum and etoposide had not demonstrated a survival benefit, according to Das. The incorporation of immune checkpoint inhibitors has now established a new therapeutic standard in this setting, offering improved survival outcomes for a patient population historically associated with poor prognoses, she highlighted.

In patients with LS-SCLC, recent evidence supports the use of consolidation immunotherapy following completion of chemoradiation, Das said. The phase 3 ADRIATIC trial (NCT03703297), data from which were presented at the 2024 ASCO Annual Meeting, investigated the role of durvalumab in this context. In this study, patients with limited-stage disease who had not experienced disease progression after definitive chemoradiation were randomly assigned to receive either durvalumab or placebo for up to 2 years. The trial demonstrated statistically significant improvements in both overall survival and progression-free survival for patients treated with durvalumab. Based on these findings, 

 for use in the consolidation LS-SCLC setting in December 2024. The agent is now routinely offered to patients with LS-SCLC who have completed chemoradiotherapy and remain without disease progression, Das concluded.

Videos

Millie Das, MD, discusses first-line standards of care for patients with extensive-stage and limited-stage small cell lung cancer.

Dr Das on the ALINA Trial in Early-Stage ALK+ Lung Cancer

Millie Das, MD, member, Stanford Cancer Institute; clinical professor, Department of Medicine, Med/Oncology, Stanford Healthcare, discusses 3 key clinical trials that have advanced treatment for patients who present with non–small cell lung cancer (NSCLC).

The first of these 3 studies is the phase 3 ALINA trial (NCT03456076), which investigated adjuvant alectinib (Alecensa) in early-stage resected 

-positive lung cancer, Das begins. The trial demonstrated a significant disease-free survival benefit with alectinib compared with chemotherapy, 

, she says. Das adds that this approval provided an effective new treatment option for eligible patients.

 were presented during the plenary session at the 

 Das continues, noting that the presentation received a standing ovation at the conference. Patients with unresectable stage III 

-mutant lung cancer who had undergone chemoradiation were randomly assigned to receive either osimertinib (Tagrisso) orplacebo, she reports. The results showed a significant benefit for those receiving osimertinib, leading to widespread anticipation of its approval for patients with 

-mutant lung cancer following chemoradiation, Das says. Although not yet approved, a supplemental new drug application seeking the approval of osimertinib was 

However, data with neoadjuvant osimertinib remains limited, Das states. In a multi-institutional trial (NCT03433469) of 27 patients with surgically resectable stage I-IIA 

-mutant NSCLC, osimertinib did not achieve the desired major pathologic response rate, with only a 15% response rate observed in the intention-to-treat analysis, Das reports. Patients enrolled onto this trial received osimertinib 1 to 2 months prior to surgery. This lower-than-expected response rate highlights the need for further research, she states.

There is growing interest in combining osimertinib with chemotherapy in the neoadjuvant setting, an approach being explored in the ongoing phase 3 NeoAdora trial (NCT04351555), Das adds. This combination aims to improve outcomes and provide more effective treatment strategies for patients with 

Millie Das, MD, discusses key trials that have advanced treatment for patients who present with non–small cell lung cancer.


Millie Das, MD, of Stanford Cancer Center, discusses the progress in small cell lung cancer treatment.

Progress in SCLC: From Deadly to Cure?

Millie Das, MD, clinical associate professor, medicine/oncology, member, Stanford Cancer Center, chief, oncology, Palo Alto VA, member, VA national Lung Cancer Working Group, Lung Cancer Precision Oncology Program, discusses the current landscape of new and emerging ADCs under investigation in small-cell lung cancer (SCLC), as well as highlights the phase 2 SWOG S1929 study (NCT04334941) in extensive-stage SCLC.

As one of the newest drug classes to emerge within the lung cancer space, there is significant interest in harnessing the efficacy of ADCs for patients with SCLC, Das begins. A number of ADCs are currently in development in this disease space, including the B7-H3-targeted agent ifinatamab deruxtecan (DS-7300), sacituzumab govitecan-hziy (Trodelvy), and the combination of atezolizumab (Tecentriq) plus talazoparib (Talzenna), Das reports.

The combination of atezolizumab plus talazoparib was recently evaluated in the phase 2 SWOG S1929 study in patients with extensive-stage SCLC who expressed Schlafen-11 (SLFN11), Das continues. Patients were randomly assigned to maintenance atezolizumab or maintenance atezolizumab plus talazoparib (AT) following treatment with frontline chemotherapy, she details. Notably, prior studies demonstrated that SLFN11 expression may be able to predict improved clinical outcomes with the PARP inhibitor veliparib (ABT-888) in combination with temozolomide.

Results from this trial were presented at the 2023 ASCO Annual Meeting, and showed that the addition of talazoparib to standard-of-care maintenance atezolizumab improved progression-free survival (PFS) in SLFN11-positive patients, Das states. The median PFS was 2.8 months with atezolizumab alone vs 4.2 months with the combination at a median follow-up of 5 months. Although minimal preliminary improvements in OS were observed, these data are immature.

However, overall response rates were numerically lower, at 12% with the combination and 16% with the monotherapy. Similarly, disease control rates were 69% and 59% with the monotherapy and combination, respectively.

Regarding safety, hematologic toxicity was slightly increased with the combination as expected. The most common adverse effect was grade 3 anemia. Additionally, treatment discontinuation due to toxicities did not increase in either arm.

The success of this trial demonstrated the viability and feasibility of prospective biomarker selected trials within SCLC, and suggested that these trials should pave the way forward, Das concludes.

Millie Das, MD, discusses the current landscape of new and emerging ADCs under investigation in small-cell lung cancer and highlights the phase 2 SWOG S1929 study.

Millie Das, MD

Articles

Dr Das on Updates to the Standard First-Line Treatment Paradigm for ES-SCLC

Dr Das on the ALINA Trial in Early-Stage ALK+ Lung Cancer

Progress in SCLC: From Deadly to Cure?

Dr Das on the Landscape of Current and Emerging ADCs in SCLC