Promising Advances in Lung Cancer Treatment: Insights from the TORG1937 (DATE) Study on Durvalumab Timing

Study Overview

The study titled "Phase II study of durvalumab immediately after completion of chemoradiotherapy in unresectable stage III non-small-cell lung cancer: TORG1937 (DATE study)" investigated the efficacy and safety of administering durvalumab immediately after concurrent chemoradiotherapy (CCRT) in patients with unresectable stage III non-small-cell lung cancer (NSCLC) (1).

This prospective, single-arm, open-label phase II clinical trial focused on patients who did not experience disease progression after definitive CCRT, which included two cycles of platinum-based doublet chemotherapy with 60 Gy/30 Fr radiotherapy. These patients received durvalumab every 2 weeks for up to 12 months, starting from the next day (up to 5 days) after their final radiation dose.

The study enrolled 50 patients from January 2020 to August 2020, of which 47 were evaluable for treatment efficacy and safety. The primary endpoint of the study was the 1-year progression-free survival (PFS) from the time of registration before the start of CCRT. The results showed that the 1-year PFS from registration was 75.0%, with a 60% confidence interval (CI) of 69.0 - 80.0 and a 95% CI of 59.4 - 85.3. Additionally, the objective response rate throughout the study treatment was 78.7%, and the median PFS from registration was 14.2 months (95% CI, 13.4 to not reached). The incidences of Grade 3/4 pneumonitis and febrile neutropenia were each noted to be 4.3%.

The study's conclusion highlighted that the primary endpoint was met. It indicated that the incidence of pneumonitis was comparable to that observed in the Japanese subset of the PACIFIC study. The data support the efficacy and safety of durvalumab administered immediately after the completion of CCRT for patients with unresectable stage III NSCLC. The clinical significance of these findings lies in providing an effective and safe treatment option for a specific patient population, potentially improving their clinical outcomes.

Standard Treatment

The standard treatment for unresectable stage III non-small-cell lung cancer (NSCLC) involves concurrent chemoradiotherapy (CCRT), followed by consolidation therapy with durvalumab. This approach became standard following the results of the PACIFIC trial, which demonstrated a significant improvement in progression-free survival (PFS) and overall survival (OS) with the addition of durvalumab after CCRT.

The TORG1937 (DATE) study further investigates this treatment paradigm, specifically exploring the efficacy and safety of administering durvalumab immediately after the completion of CCRT. The study's results showing a 1-year PFS rate of 75% and an objective response rate of 78.7% are quite promising, especially considering the historically poor outcomes associated with unresectable stage III NSCLC.

The impact of these results can be considered significant for several reasons:

  1. Early Administration of Durvalumab: The study offers valuable insights into the optimal timing of durvalumab administration post-CCRT. Starting immunotherapy immediately after CCRT could potentially maximize the therapeutic effect by targeting minimal residual disease.

  2. Safety Profile: The reported incidences of Grade 3/4 pneumonitis and febrile neutropenia (each at 4.3%) are consistent with previous findings, suggesting that the early administration of durvalumab does not significantly increase severe side effects.

  3. Clinical Relevance: For patients with unresectable stage III NSCLC, improving PFS is crucial. The study's findings may influence clinical practice by further refining the timing of durvalumab therapy post-CCRT, potentially leading to better patient outcomes.

  4. Basis for Future Research: These results can form the basis for larger, randomized controlled trials to validate the findings and potentially redefine the standard treatment protocol.

In summary, while the standard treatment involving CCRT followed by durvalumab is already established, the TORG1937 (DATE) study contributes valuable data on the timing of immunotherapy initiation, suggesting a potentially impactful approach in treating unresectable stage III NSCLC. However, larger and more comprehensive studies would be needed to confirm these findings and fully assess their impact on clinical practice.

Clinical Impact Potential

The clinical impact potential of the TORG1937 (DATE) study can be assessed as medium. This assessment is based on several key factors:

  1. Incremental Improvement in Treatment Strategy: The study explores optimizing the timing of an already established treatment (durvalumab) following CCRT. While the early administration of durvalumab shows promising results, it represents an incremental improvement rather than a groundbreaking change in the treatment of unresectable stage III NSCLC.

  2. Consistency with Existing Safety Profile: The safety profile observed in the study, with Grade 3/4 pneumonitis and febrile neutropenia rates comparable to existing data, suggests that this approach does not introduce significant new risks. This consistency is positive but does not drastically alter the current understanding of the treatment’s safety.

  3. Need for Larger, Randomized Trials: The study's findings, while promising, are from a single-arm, phase II trial. For a high clinical impact, randomized controlled trials with larger patient populations are typically required to validate these results and establish a new standard of care.

  4. Potential to Refine Current Treatment Protocols: The study provides important insights that could refine the timing of durvalumab therapy, potentially leading to improved patient outcomes. This aspect underlines its medium impact, as it contributes to optimizing existing treatment protocols rather than introducing a new treatment modality.

  5. Focus on a Specific Patient Population: The study’s impact is specifically targeted at patients with unresectable stage III NSCLC, a subgroup within the broader lung cancer patient population. This specificity slightly limits the overall impact scope.

In conclusion, the TORG1937 (DATE) study has a medium clinical impact potential, offering valuable insights that could refine existing treatment protocols for unresectable stage III NSCLC. However, further research, particularly through larger, randomized trials, is necessary to fully establish the clinical significance of the findings and their impact on standard treatment practices.

Reference

Nakamichi S, Kubota K, Misumi T, Kondo T, Murakami S, Shiraishi Y, Imai H, Harada D, Isobe K, Itani H, Takata S, Wakui H, Misumi Y, Ikeda S, Asao T, Furuya N, Hosokawa S, Kobayashi Y, Takiguchi Y, Okamoto H. Phase II study of durvalumab immediately after completion of chemoradiotherapy in unresectable stage III non-small-cell lung cancer: TORG1937 (DATE study). Clin Cancer Res. 2024 Jan 2. doi: 10.1158/1078-0432.CCR-23-2568. Epub ahead of print. PMID: 38165684.