IASLC 19th WCLC: highlights and the biggest headlines

In this round up we provide you with the biggest headlines and highlights from the IASLC World Conference on Lung Cancer (WCLC) (Toronto, Canada, September 23–26 2018), the world’s largest meeting dedicated to lung cancer and other thoracic malignancies. Highlights include:

NELSON: CT screening reduces lung cancer mortality by 26% in men

IMpower133: Atezolizumab prolongs survival

PACIFIC: durvalumab improves OS for NSCLC

Dogs are able to reliably sniff out malignant pulmonary nodules, study shows

NELSON: CT screening reduces lung cancer mortality by 26% in men

Findings from the NELSON study demonstrate that CT screening among asymptomatic men, who are at high risk for lung cancer, led to a 26% reduction in lung cancer deaths at 10 years of study follow-up.

In the smaller subset of women, the rate-ratio of dying from lung cancer varied between 0.39 and 0.61 in different years of follow-up, indicating an even significant and larger reduction in lung cancer mortality than in men.

More information on the NELSON study

The NELSON study is a population-based, controlled trial that enrolled 15,792 individuals, who were randomized 1:1 to either the study arm or control arm. Study arm participants were offered CT screenings at baseline, 1, 3 and 5 and 0.5 years after randomization. No screenings were offered to control arm participants. Participants’ records were linked to national registries with 100% coverage regarding cancer diagnosis (Netherlands Cancer Registry), date of death (Centre for Genealogy) and cause of death (Statistics Netherlands).

A panel of experts reviewed 65% of cases. The follow-up period comprised a minimum of 10 years, unless deceased, for 93.7% of enrolled participants.

The results of the study showed an 86% average CT screening compliance rate, encompassing 29,736 scans. In 9.3% of participants, additional CT scans were performed within 2 months to estimate nodule volume doubling time, leading to an overall referral rate of 2.3% for suspicious nodules. Detection rates across the rounds varied between 0.8 and 1.1%, and 69% of screen-detected lung cancers were detected at Stage 1A or 1B. A total of 261 lung cancers (52 interval cancers) were detected before the fourth round of follow ups. In a subset of analyzed patients, surgical treatment was three times significantly more prevalent in study lung cancer patients than in control arm patients (67.7% versus 24.5%).

“These findings show that CT screenings are an effective way to assess lung nodules in people at high risk for lung cancer, often leading to detection of suspicious nodules and subsequent surgical intervention at relatively low rates and with few false positives, and can positively increase the chances of cure in this devastating disease,” explained Harry J De Koning (Erasmus MC, Rotterdam, Netherlands).

“It is the second largest trial in the world, with an even more favorable outcome than the first trial, the NLST, showed. These results should be used to inform and direct future CT screening in the world,” De Koning concluded.

Source: IASLC 19th WCLC press release

IMpower133: Atezolizumab extends survival for extensive-stage small-cell lung cancer

Genentech’s (CA, USA) TECENTRIQ® (atezolizumab), an immunotherapy aimed at extensive-stage small-cell lung cancer (ES-SCLC) patients, has been announced to significantly improve overall survival (OS) and progression-free survival (PFS) when combined with standard-of-care chemotherapy as a first-line therapy – in the Phase III trial IMpower133.
[accordions ]
[accordion title=”More information on IMpower133:” load=”hide”]IMpower133 involved 403 chemotherapy-naïve patients and the end-points were OS and PFS. The monoclonal antibody atezolizumab plus chemotherapy (carboplatin and etoposide) was administered to 201 previously-untreated ES-SCLC patients in 1200 mg doses, intravenously, on day 1 of the four 21-day cycles of the trial.

Meanwhile, 202 patients received placebo plus chemotherapy in an identical fashion. Once the cycles were complete, a maintenance phase of atezolizumab or placebo was continued until progressive disease, respectively. Whilst prophylactic cranial irradiation was allowed during the maintenance phased of the trial, thoracic radiation was not.[/accordion]

The data cut-off was at 13.9 months, and the median OS of the atezolizumab arm was 12.3 months, which was significantly higher than the 10.3-month median OS of the placebo arm. The 1-year overall survival rate was 51.7% in the atezolizumab group, compared to 38.2% in the placebo group. No new safety profile concerns were raised.

“This is the first study in 30 years to show a significant improvement in survival in the first line treatment of this highly lethal disease. This is an exciting time in oncology, and we are thrilled to finally see real progress in the SCLC space,” explained Stephen V. Liu from Georgetown University (DC, USA).

Sources: Horn L, Mansfield AS, Szczęsna A et al. First-line atezolizumab plus chemotherapy in extensive-stage small-cell lung cancer. N. Engl. J. Med. doi: 10.1056/NEJMoa1809064 (2018). (Epub ahead of print);  WCLC press releaseGenentech press release 

PACIFIC: durvalumab improves OS for NSCLC

Findings from the PACIFIC study were announced during the conference, demonstrating that the PD-L1 inhibitor IMFINZI® (durvalumab) significantly improved OS compared with placebo for patients with Stage III, unresectable non-small cell lung cancer (NSCLC) who have not progressed following chemoradiotherapy (CRT).

These results are significant because PACIFIC is the first trial to show a survival advantage following CRT in this patient population.

More information on the PACIFIC trial

The randomized, double-blinded, placebo-controlled, multicenter trial included 713 patients in 235 study centers across 26 countries. Of the 709 patients who received treatment, 473 received durvalumab and 236 placebo.

After discontinuation, 41% and 54% in the durvalumab and placebo groups, respectively, received subsequent anticancer therapy; overall, 8% and 22.4% received another immunotherapy.

The trial showed that durvalumab significantly improved OS versus placebo, with the median not reached and 28.7 months, respectively.

Furthermore,durvalumab improved OS in all pre-specified subgroups and improved secondary endpoints of time to death or distant metastasis (TTDM), time to second progression (PFS2), time to first subsequent therapy or death (TFST) and time to second subsequent therapy or death (TSST).

Previously reported PACIFIC results showed that durvalumab significantly improved the first primary endpoint of PFS versus placebo, and updated PFS remained similar, with medians of 17.2 and 5.6 months with durvalumab and placebo, respectively. Durvalumab improved the updated TTDM, as well as PFS2, TFST and TSST.

“Results of PACIFIC provide compelling evidence for the unprecedented benefit of durvalumab treatment as the standard of care in this patient population,” explained Scott J Antonia (Moffitt Cancer Center & Research Institute and University of South Florida College of Medicine both FL, USA), who presented the findings at the conference.

“Durvalumab offers the first major advance in this disease setting in many years, offering new hope to patients with Stage III, unresectable NSCLC without progression after CRT,” Antonia added.

Source: IASLC 19th WCLC press release

Dogs are able to reliably sniff out malignant pulmonary nodules, study demonstrates

A further study presented as the conference demonstrated the reliability of trained dogs in identifying malignant pulmonary nodules. In this study, the team sought to investigate the potential of trained dogs in discriminating malignant and benign pulmonary nodules. Exhaled air samples were collected from 30 patients with indeterminate pulmonary nodules before diagnostic and therapeutic surgery, and 77 individuals with neither lung cancer nor pulmonary nodules.

Researchers presented the dog, trained via a reward-based method on the association of smell patterns, with air samples of an approximate ratio of 1:4, presence of pulmonary nodules to absence of pulmonary nodules, to be marked according to malignancy.

The dog successfully identified malignant samples with a sensitivity of 0.97, a specificity of 0.99, a predictive positive value of 0.97 and a predictive negative value of 0.99.

Twenty-seven of 30 nodules were correctly identified as lung cancer-positive, verified by the outcomes of pathology reports.

“Having previously established that trained dogs can sniff out the presence of lung cancer in exhaled gas samples, we are thrilled to identify the ability to differentiate between malignant or benign nodules as well,” explained Angela Guirao (Hospital Clínic Barcelona, Spain). “These discoveries underscore an opportunity to improve the early detection of lung cancer and malignant nodules, pairing trained dogs with established technology for accurate diagnoses.”

Source: IASLC 19th WCLC press release