Luis Paz-Ares, MD, PhD
At the 2019 ESMO Congress, updated information from the phase III CASPIAN trial demonstrated delays in the improvement of new lesions and improvements in patient-reported outcomes (PROs) with the addition of durvalumab (Imfinzi), a PD-L1 inhibitor, to etoposide and platinum-primarily based chemotherapy in the frontline for sufferers with comprehensive-stage little cell lung cancer (ES-SCLC).1 However, PD-L1 expression did not seem predictive of response.
General, 805 sufferers with previously untreated ES-SCLC had been randomized 1:1 to get either four cycles of etoposide and platinum-primarily based chemotherapy plus durvalumab (1500 mg) every single three weeks followed by upkeep durvalumab every single four weeks, or up to six cycles of the etoposide plus platinum-primarily based chemotherapy regimen alone every single three weeks, plus prophylactic cranial irradiation (PCI) per the investigator’s discretion.
Prior benefits of the CASPIAN trial presented at the 2019 Planet Conference on Lung Cancer demonstrated that there was an enhance in all round survival (OS) with the addition of durvalumab median OS was 13. months versus 10.three months in the durvalumab arm versus the handle arm, translating to a 27% reduction in the threat of death (HR, .73 95% CI, .591-.909 P = .0047) at a median adhere to-up of 14.two months.two
The updated findings demonstrated that fewer sufferers in the durvalumab arm created new lesions at very first progression (41.four% vs 47.two%). The prices of total progression events had been 84.three% versus 86.six% in the durvalumab versus handle arms, although progression occurred in 71.six% and 72.1% of sufferers, respectively. Prices of nontarget lesion progression had been 24.six% and two.7%, although death in the absence of progression occurred in 12.7% and 14.five%, respectively.1
In an interview with Targeted Oncology, Luis Paz-Ares, MD, PhD, healthcare oncologist and chair of Health-related Oncology Division at Hospital Doce de Octubre in Madrid, Spain, discussed the findings for the CASPIAN trial that had been presented at the 2019 ESMO Congress. He also addressed what subsequent actions are important to additional create the durvalumab mixture in this setting.
TARGETED ONCOLOGY: What was the rationale for the CASPIAN trial?
Paz-Ares: The CASPIAN trial really looked at the effects of adding an anti–PD-L1 agent to the typical platinum-primarily based chemotherapy mixture in sufferers with sophisticated ES-SCLC. For a quantity of years, nearly three decades, either carboplatin or cisplatin had been the typical of care in this setting. Not too long ago, we have observed that PD-1/PD-L1 inhibitors do have some intriguing activity in lung cancer, particularly in SCLC as properly. In reality, final year there was a study displaying that adding atezolizumab (Tecentriq), one more PD-L1 inhibitor, did enhance survival in sufferers with this illness. This trial really attempted to evaluate the part of durvalumab, a PD-L1 inhibitor, as a combining therapy with chemotherapy in this setting.
TARGETED ONCOLOGY: What had been efficacy information for the addition of durvalumab?
Paz-Ares: What we have observed in this trial at the interim evaluation is the durvalumab arm of four courses of platinum-primarily based chemotherapy plus etoposide plus durvalumab followed by durvalumab, demonstrated escalating survival as compared to the handle arm, which was platinum plus etoposide for up to six courses followed, by the investigators criteria, with PCI, or not. The key endpoint was met, escalating OS with a common enhance in the hazard ratio of .73, which translates to an enhance the median OS from 10.three months in the handle arm to 13 months in the experimental arm.
TARGETED ONCOLOGY: What had been the significance of these information?
Paz-Ares: It is clear that anti–PD-L1 therapy is productive. The information from the CASPIAN trial are somehow [associated with] the IMpower133 trial with atezolizumab, so 1 trial confirms the other as a notion [that there is] enhanced survival, enhanced PFS, enhanced response price, and the toxicity profile is manageable. There are no unexpected adverse effects.
The second point that is relevant from that distinct trial is all sufferers received cisplatin and carboplatin, per investigator’s option. This is somewhat reflective of what is taking place in actual life. Secondly, we let sufferers to get therapy in the handle arm right after six courses of chemotherapy, which is anything we do really regularly. Thirdly, and vital as properly, sufferers with asymptomatic brain metastases had been under 20% without having irradiation. These are some added bits to this study that I feel will have some influence.
How relevant is this for the patient? General, [the addition of durvalumab] decreased the threat of death by 27%. I feel this is vital. We enhanced survival by practically three months. I would choose it to be three years, but these information, I feel, are relevant.
TARGETED ONCOLOGY: Could you speak to progression in sufferers with PD-L1 expression?
Paz-Ares: Primarily, these information say that in terms of PD-L1 expression, the expression of PD-L1 in our evaluation in the tumor cells was definitely low and did not let us to make any [conclusions]. I do not feel PD-L1 expression is going to be an productive biomarker to pick sufferers in this setting.
Secondly, in terms of progression, I would say the anti–PD-L1 therapy of durvalumab added to chemotherapy decreased the progression prices of all locations, which includes the central nervous technique. Thirdly, in terms of PROs, the information are fairly important, and I would say the therapy with durvalumab did not impair high quality of life for these sufferers.
TARGETED ONCOLOGY: What would you say are the quick subsequent actions with this analysis?
Paz-Ares: There are a lot of factors to do. Regarding this distinct trial, it is really vital to get mature information. It is going to be definitely vital to see how substantially durvalumab is adding in terms of extended-term survival. Second, what occurred with the durvalumab plus chemotherapy arm, the third arm? The interim analyses had been not reaching the threshold for significance, but we have to have to wait till the final evaluation. That is an vital point as properly. Third, it would be good to see additional biomarker information to see if we are in a position to get some predictivity right here.
Lastly, in terms of the context of NSCLC, a quantity of other factors have to be carried out. We’ve observed PD-1/PD-L1 inhibitors in earlier illness in the context of restricted illness stage, specifically in mixture with chemoradiotherapy. Secondly, some other options of immunotherapy are going to be essential right here. Some of the eye-catching therapies would be, I feel, from a rational point of view, bispecifics against the LL3 and anti-CD3. There is currently 1 compound in clinical phase I trials. Of course, we have to find out a lot about the immune milieu of SCLC, such as which are the prospective targets that we need to target in this setting. Other agents have to be additional investigated.
- Paz-Ares L, Goldman JW, Garassino MC, et al. PD-L1 expression, patterns of progression and patient-reported outcomes (PROs) with durvalumab plus platinum-etoposide in ES-SCLC: Outcomes from CASPIAN. Presented at 2019 ESMO Congress September 27-October 1, 2019 Barcelona, Spain. Abstract LBA62.
- Paz-Ares L, Chen Y, Reinmuth N, et al. General survival with durvalumab plus etoposide-platinum in very first-line comprehensive-stage SCLC: benefits from the CASPIAN study. Presented at: International Association for the Study of Lung Cancer 20th Planet Conference on Lung Cancer September 7-10, 2019 Barcelona, Spain. Abstract OA002.