Local Therapy Developments Hold Promise for Survival Improvements for NSCLC

Clinicians have been observing significant improvements in lung cancer treatment with the availability of new therapies, explained speakers in a session at the 2024 World Conference on Lung Cancer (WCLC). Held from September 7 to September 10 in San Diego, California, the WCLC speakers discussed new cutting-edge innovations for local therapies as well as the benefits of moving therapies to early and local-regional non–small cell lung cancer (NSCLC).¹

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Carlos Gil Ferreira, MD, PhD, president of the Oncoclinicas Institute and chief medical officer at Oncoclinicas in Brazil, discussed local therapies for metastatic NSCLC (mNSCLC), noting that data have suggested that radiotherapy could improve survival outcomes for individuals with mNSCLC who had patterns of oligoprogression following first-line immune checkpoint inhibitors.¹ In a cohort study published in JTO Clinical and Research Reports, investigators evaluated patients with mNSCLC who had progressed following PD-(L)1 inhibitors, with or without chemotherapy. They evaluated the frequency and location of oligoprogression and assessed the overall survival (OS) with radiotherapy.^1,2

The entire cohort consisted of 159 individuals, with 64 in the oligoprogression cohort. The subgroup had a median age of 69 years, with 54.8% with adenocarcinoma, 28.4% with squamous cell carcinoma, and 17.7% with another type of tumor. Approximately 43.5% had received immunotherapy and 56.5% received chemotherapy. Investigators noted that brain metastases were associated with an increased likelihood of oligoprogression and liver metastases were associated with a decreased likelihood, according to the presentation.¹

“Oligoprogression is common in the primary lung brain and bone following first-line ICI therapy,” Ferreira said. “Presence of brain metastases at baseline Is predictive of oligoprogression.”¹

Investigators concluded that those who received radiotherapy had a longer median progression-free survival 2 (PFS2) at 17 months compared with 11.5 months with those who did not, and a longer OS at 23 months compared with 13 months, respectively. However, there were no improvements for PFS2 and OS for systemic progressive disease.¹

In a similar analysis from a phase 2 trial, investigators used a strategy to analyze the local therapy. Investigators aimed to determine if the impact of ablation to oligo-residual disease impacted the survival benefit of ICIs for patients with advanced disease. According to the presentation, it is unclear whether ablation improves survival benefit of ICIs. In the study, investigators included patients who achieved oligo-residual disease on ICI who had advanced mNSCLC, had a first line immunotherapy (with or without chemotherapy), and had residual lesions suitable for complete ablation. Treatment for 137 individuals was randomized for either maintenance immunotherapy or local ablation therapy to residual sites and resumption of immunotherapy until either progressive disease or patients’ consent was withdrawn. Ferreira noted that only half of the individuals were included for the preliminary analysis.¹

The median PFS was 26.7 months for ablation compared with 11.7 months with ICIs, and median OS was not estimated at this time compared with 32.8 months, respectively.¹

“They did a subgroup [exploratory] analysis [on] the strategy of ablation, cryoablation, [or] thermal ablation,” Ferreira said. “There is an advantage for cryoablation, but it is too early to draw any conclusions.”¹

As for other local therapies, Paula Ugalde, MD, associate professor of surgery at Harvard Medical School, discussed early and local-regional therapies. The first trial she discussed, NADIM trial (NCT03081689), demonstrated robust clinical evidence of perioperative chemo-immunotherapy with nivolumab at 5 years, with PFS at 5 years of 65% and OS at 5 years being 69.3%. There were also no signs of late toxicity or treatment-related deaths, according to the WCLC presenters.¹

Furthermore, data for EYNOTE-671 (NCT03425643) showed the neoadjuvant pembrolizumab and chemotherapy had greater pathologic regression based on percent residual viable tumor (%RVT) compared to the placebo and chemotherapy, with median rates being 29.5% and 52%, respectively. Higher %RVT was associated with poorer event-free survival, regardless of treatment arm, according to Ugalde. As for data from Impower010 (NCT02486718), the 5 or more years of follow-up data showed that patients with stage II-IIIA PD-L1 expression of more than 1% of tumor cells and more than 50% of tumor cells treated with atezolizumab demonstrated disease free survival and OS outcomes compared with those in the best supportive care arm, regardless of disease stage or regional lymph node stage.¹

In the final study presented by Ugalde at WCLC, CHIO3 (NCT04062708), Ugalde explained that 29 individuals enrolled had clinical N2 disease, with 72.4% reduced to N0 with neoadjuvant durvalumab and chemotherapy, which doubled the rates of N2 nodal clearance for patients who had operable stage 3A/B NSCLC.¹

“We need to continue to discuss patients with stage III disease, independent of the volume of the mediastinal disease, with our colleagues from medical oncology,” Ugalde concluded.¹

REFERENCES

1. Ferreira CGM, Rolfo C, Figueroa PU, Sands J. HOD01 - Highlights of the Day - Sunday Abstracts. World Conference on Lung Cancer; San Deigo, California. September 7 to September 10, 2024.

2. Kroeze SGC, Schaule J, Fritz C, et al. Metastasis directed stereotactic radiotherapy in NSCLC patients progressing under targeted- or immunotherapy: efficacy and safety reporting from the 'TOaSTT' database. Radiat Oncol. 2021;16(1):4. Published 2021 Jan 6. doi:10.1186/s13014-020-01730-0