LCMC3 results point to early NSCLC response with neoadjuvant atezolizumab
medwireNews: Two cycles of neoadjuvant atezolizumab may benefit patients with resectable non-small-cell lung cancer (NSCLC), indicate findings from the LCMC3 study presented at the IASLC 2020 World Conference on Lung Cancer.
Jay Lee (David Geffen School of Medicine at UCLA, Los Angeles, California, USA) explained that the phase 2 trial recruited patients without EGFR- or ALK-activating mutations who had stage IB–IIIA NSCLC or stage IIIB disease without mediastinal organ invasion.
“This study provides additional clinical evidence for the ongoing placebo-controlled phase III IMpower030 study of atezolizumab combined with platinum-based chemotherapy,” he commented.
The trial’s protocol states up to two cycles of atezolizumab 1200 mg at 3-week intervals followed by surgery within 8–28 days of completing neoadjuvant therapy, and then surveillance with an optional 12 months of atezolizumab treatment.
Lee described the 181 participants as representative of their disease population, with an average age of 65 years, 51% being female, and 90% being current or former smokers. In addition, 38% had squamous disease and a range of PD-L1 tumor proportion scores (TPS), with 29% testing high (≥50%), 17% medium (1–49%), and 38% low (<1%), while 17% had an unknown TPS.
Overall, 171 patients completed both cycles of atezolizumab and 159 patients went on to receive surgery; 15 patients were subsequently excluded from the analysis after detection of an EGFR- or ALK-activating mutation.
Among the 144 patients in the primary efficacy population, the primary endpoint of major pathologic response – defined as no more than 10% viable tumor cells – was reached by 21%, and a further 7% of patients achieved a pathologic complete response.
In addition, 155 patients were reassessed for clinical and pathologic staging after atezolizumab therapy, with downstaging reported for 43% and upstaging for 19%.
Despite the study protocol dictating a tighter time window for surgery, compared with that of other neoadjuvant trials, 88% of the patients who underwent surgery did so within the planned time, at a median of 22 days after completing atezolizumab, Lee reported.
Of the patients who had delayed surgery, just four were for treatment-related reasons, six were for other medical reasons, and nine for logistical issues, he noted.
Most (79%) of the patients underwent lobectomy and just 15% of the 101 patients who had minimally invasive procedures required a conversion to thoracotomy. R0 surgery was achieved for 92% of patients, a rate described by Lee as being “comparable, if not superior” to those reported for other trials of preoperative chemotherapy in this patient population.
Intra-operative complications were “rare” with bronchial and vascular complications reported for 1% and 3% of patients, respectively, and all complications were corrected in the same procedure, the presenter said. The median hospital stay of 7.5 days was comparable to that in earlier trials and there was just one sudden death unrelated to treatment within 30 days of surgery and one pneumonitis death within 30–90 days.
Furthermore, just 6% of patients had treatment-related adverse events of grade 3 before surgery and after surgery this rose to 11%, with grade 4 and 5 events at this time occurring in 2% and 1%, respectively. Immune-related adverse events were also uncommon at grade 3, affecting 2% before and 7% after surgery, with individual cases of grade 4 and 5 postoperatively.
Finally, Lee reported “favorable” exploratory survival analyses, with 1-year rates of progression-free and overall survival for patients with stage I or II disease of 85% and 92%, respectively, and corresponding rates for stage III patients of 85% and 95%.
These results might point to a “survival advantage compared with historical information,” the presenter commented.
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