Real-world data support new SOC in patients with SCLC

The retrospective chart review IFCT 1905-CLINATEZO (NCT04920981), assessing the safety and effectiveness of chemotherapy plus atezolizumab in patients with small cell lung cancer (SCLC) demonstrated similar survival outcomes of this regimen in the real world as did the IMpower133 trial in the clinical trial setting [1]. The results of IFCT 1905-CLINATEZO were presented by Dr Lionel Falchero (Hôpitaux Nord-Ouest, Service de Pneumologie et Cancérologie Thoracique, Villefranche-Sur-Saone, France) at the American Society of Clinical Oncology (ASCO) Annual Meeting 2023, held 2-6 June 2023 in Chicago, IL, USA [2].

Medicom Medical Publishers spoke with senior author Prof. Nicolas Girard (Institut du Thorax Curie Montsouris, Institut Curie, Paris, France) to learn more.

The IFCT 1905-CL INATEZO study included 1,402 patients with extensive-stage SCLC who were treated with the combination regimen of chemotherapy and atezolizumab to evaluate the real-world safety and effectiveness of this first-line therapy and to examine subsequent treatment sequences. The presented abstract included findings from 518 patients who received chemotherapy plus atezolizumab between May 2019 and January 2020 in France. The majority of this population was male (66%) and the mean age was 65.7 years. Brain metastases were observed in 27% of the patients and 89% of the patients had a performance status of 0 or 1. A minority of the patients had received at least one previous treatment (10.6%). Furthermore, the median number of received atezolizumab injections was 7 and the median duration of treatment was 4.9 months.

Regarding effectiveness, a complete response was reached by 3.9% of the patients and a partial response was achieved by 77.1% of the patients. An additional 10.2% had stable disease. The patients were followed for a median duration of 30.8 months, after which a median overall survival (OS) of 11.3 months was reported. The corresponding 12-month and 24-month OS rates were 46.7% and 21.2%, respectively. The median OS in patients who had received a prior therapy appeared to be somewhat higher, with 14.9 months. Next, the median progression-free survival time was 5.2 months. The majority of patients would receive a subsequent therapy (66.4%).

Medicom Medical Publishers interviewed prof. Girard to learn about these findings in further detail and to find out what these results mean for daily practice

The real-world IFCT 1905-CLINATEZO study compared survival outcomes of the phase 3 IMpower133 trial to those of patients with extensive-stage SCLC in the real world. What did the IMpower133 trial set out to define and what were the results?  

“The IMpower133 trial is a placebo-controlled phase 3 trial that compared a combination of atezolizumab plus standard of care chemotherapy with platinum etoposide to chemotherapy alone in patients with extensive-stage SCLC,” responded Prof. Girard. “The integration of only four cycles of immunotherapy plus chemotherapy, followed by maintenance with atezolizumab alone, is a very new concept in this disease.” He explained that the number of chemotherapy cycles is reduced, whereas maintenance therapy with immunotherapy is being introduced in the management of extensive-stage SCLC. “The trial demonstrated survival benefits with the addition of immunotherapy to chemotherapy in this setting, continued Prof. Girard. “Patients moved from a median OS of 10 months with chemotherapy alone to 12 months with the addition of atezolizumab.” Dr Girard added that a relatively small increase in median overall survival is seen, but that there are long-term survivors as well. “This is something we did not see with chemotherapy alone.”

Your study group looked at the French cohort of patients in the IFCT 1905-CLINATEZO real-world study. Could you discuss the background of this research?

“It's always important to look at real-world data,” said Prof. Girard. “Although the IMpower 133 trial is a large study, the trial mostly included patients who had a good performance status and a relatively limited burden of disease. Therefore, we can’t be sure whether these results will be reproducible in a larger, broader population of patients. In addition, it was required by the French authorities to check the reproducibility of the findings of the Impower133 trial in the real world.“

“Our study is independent from the sponsor of the IMpower133 trial and evaluates a cohort of more than 500 patients who received atezolizumab plus chemotherapy in the setting of the so-called ‘expanded access’ program. The data demonstrates the reproducibility of the findings of the IMpower133 trial in the real world. In addition, the prognostic factors we observed appear to be different than the ones reported in the IMpower133 trial. Notably, we can see that, even in the setting of second-line treatment, more than half of the patients will gain control of the disease. This has always been a major challenge in SCLC,” emphasized Prof. Girard.

The patient characteristics show that over a quarter of the patients had brain metastases. Could you comment on that specifically?  

“For patients with brain metastasis to be eligible to be enrolled in clinical trials, they should have no symptoms,” explained Prof. Girard. “In a real-world setting, you are treating some patients with larger brain metastases and patients who have symptoms from their brain metastases. It is interesting to see that we have a high number of patients with brain metastases, because this is reflecting the real-world situation. On the other hand, approximately 90% of the patients in our study had a good performance status, just like patients who are included in clinical trials. However, this can be explained by the efficacy of immunotherapy; we know that immunotherapy beyond a performance status of 1 has limited efficacy,” clarified Prof. Girard.

What about patients who required concurrent radiotherapy? Were you able to do a sub-analysis on those patients? 

“This is actually one of the key learnings of this study,” answered Prof. Girard. “A significant proportion of patients had radiotherapy during the induction treatment with immunotherapy and chemotherapy. It mostly comprised palliative intent radiotherapy on bone metastases, but also whole brain irradiation. Furthermore, some patients received thoracic radiotherapy in the context of a significant or major partial response.” According to Prof. Girard, historical data from the CREST trial demonstrated that even in extensive-stage SCLC, if you have a very good response to induction treatment, radiotherapy on the primary tumour delivers an additional benefit in terms of overall survival [3].

Are these findings going to change your practice?  

“This real-world study confirmed that the combination of immunotherapy and chemotherapy is a new standard of care for patients with extensive-stage SCLC,” concluded Prof. Girard. “We are also able to deliver descriptives of the subsequent treatments that were administered to patients. This information was not analysed in the clinical trial. These data can help us to answer questions like: ‘What should we do with patients who have disease progression; can we rechallenge these patients? And what should we do with immunotherapy at this point? Should we maintain or discontinue immunotherapy?” These will be important questions to answer going forward, Prof. Girard concluded.

 References

1. Horn L, et al. NEJM. 2018;379:2220-2229
2. Falchero et al, Long-term effectiveness and treatment sequences in patients with extensive stage small cell lung cancer receiving atezolizumab plus chemotherapy: Results of the IFCT-1905 CLINATEZO real-world study. ASCO, June 2-6, 2023, Chicago, USA. Abstract 8583.
3. Slotman BJ, et al. Lancet. 2015;385(9962):36-42

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Posted on 10 October, 202311 October, 2023