Sacituzumab Govitecan Versus Docetaxel for Previously Treated Advanced or Metastatic Non–Small Cell Lung Cancer: The Randomized, Open-Label Phase III EVOKE-01 Study

Author(s): Luis G. Paz-Ares, MD, PhD¹; Oscar Juan-Vidal, MD²; Giannis S. Mountzios, MD, PhD³; Enriqueta Felip, MD, PhD⁴; Niels Reinmuth, MD⁵; Filippo de Marinis, MD, PhD⁶; Nicolas Girard, MD, PhD⁷; Vipul M. Patel, MD⁸; Takayuki Takahama, MD, PhD⁹; Scott P. Owen, MD¹⁰; Douglas M. Reznick, MD¹¹; Firas B. Badin, MD¹²; Irfan Cicin, MD¹³; Sabeen Mekan, MD¹⁴; Riddhi Patel, PharmD¹⁴; Eric Zhang, PhD¹⁴; Divyadeep Karumanchi, PharmD¹⁴; Marina Chiara Garassino, MD¹⁵

Source: https://doi.org/10.1200/JCO.24.0073

Dr. Maen Hussein's Thoughts

Failed? Numerical overall survival (OS) benefit for sacituzumab vs docetaxol, but not statistically significant. Better tolerated, also overall survival (OS) noticed more in patients who did not respond to antiPDL-1 therapy.

PURPOSE

The open-label, phase III EVOKE-01 study evaluated sacituzumab govitecan (SG) versus standard-of-care docetaxel in metastatic non–small cell lung cancer (mNSCLC) with progression on/after platinum-based chemotherapy, anti–PD-(L)1, and targeted treatment for actionable genomic alterations (AGAs). Primary analysis is reported.

METHODS

Patients were randomly assigned 1:1 (stratified by histology, best response to last anti–PD-(L)1–containing regimen, and AGA treatment received or not) to SG (one 10 mg/kg intravenous infusion on days 1 and 8) or docetaxel (one 75 mg/m2 intravenous infusion on day 1) in 21-day cycles. Primary end point was overall survival (OS). Key secondary end points were investigator-assessed progression-free survival (PFS), objective response rate, patient-reported symptom assessment, and safety.

RESULTS

In the intention-to-treat population (SG, n = 299; docetaxel, n = 304), 55.4% had one previous line of therapy. Median follow-up was 12.7 months (range, 6.0-24.0). The primary end point was not met. There was a numerical OS improvement for SG versus docetaxel (median, 11.1 v 9.8 months; hazard ratio [HR], 0.84 [95% CI, 0.68 to 1.04]; one-sided P = .0534), consistent across squamous and nonsquamous histologies. Median PFS was 4.1 versus 3.9 months (HR, 0.92 [95% CI, 0.77 to 1.11]). An OS benefit was observed for SG (n = 192) versus docetaxel (n = 191) in mNSCLC nonresponsive to last anti–PD-(L)1–containing regimen (3.5-month median OS increase; HR, 0.75 [95% CI, 0.58 to 0.97]); this was consistent across histologies. Among patients receiving SG and docetaxel, 6.8% and 14.2% discontinued because of treatment-related adverse events (TRAEs), respectively; 1.4% and 1.0%, respectively, had TRAEs leading to death.

CONCLUSION

Although statistical significance was not met, OS numerically improved with SG versus docetaxel, which was consistent across histologies. Clinically meaningful improvement in OS was noted in mNSCLC nonresponsive to last anti–PD-(L)1–containing regimen. SG was better tolerated than docetaxel and consistent with its known safety profile, with no new safety signals.

Author Affiliations

¹Hospital Universitario 12 de Octubre, H12O-CNIO Lung Cancer Unit, Complutense University and Ciberonc, Madrid, Spain; ²Hospital Universitari i Politécnic La Fe de Valencia, Valencia, Spain; ³Henry Dunant Hospital Center, Athens, Greece; ⁴Vall d’Hebron University Hospital and Vall d’Hebron Institute of Oncology, Barcelona, Spain; ⁵Asklepios Lung Clinic, German Center for Lung Research (DZL), Munich-Gauting, Germany; ⁶European Institute of Oncology IRCCS, Milan, Italy; ⁷Institut du Thorax Curie Montsouris, Institut Curie, Paris, France; ⁸Florida Cancer Specialists and Research Institute, Ocala, FL; ⁹Kindai University, Osaka, Japan; ¹⁰McGill University Health Centre, Montreal, QC, Canada; ¹¹Rocky Mountain Cancer Center, Aurora, CO; ¹²Baptist Health Medical Group, Lexington, KY; ¹³Istinye University, Medical Center, Istanbul, Turkey; ¹⁴Gilead Sciences, Inc, Foster City, CA; ¹⁵University of Chicago Comprehensive Cancer Center, Chicago, IL

Amivantamab Plus Lazertinib in Atypical EGFR-Mutated Advanced Non–Small Cell Lung Cancer: Results From CHRYSALIS-2

The CHRYSALIS-2, the cohort C analysis of patients with atypical EGFR mutations showed meaningful and durable activity. Atypical mutations can be difficult to deal with as a clinician, and having concrete data on these (S768I, L861Q and G719ZX) mutations gives assurance that this doublet is active. Overall response rate (ORR) was 52% and median progression-free survival (PFS) was 11.1 months in refractory patients and 19.5 months in the treatment-naive population.

Survival with Osimertinib plus Chemotherapy in EGFR-Mutated Advanced NSCLC

The final overall survival (OS) analysis from the FLAURA2 confirms the well-published findings that Osi + chemo improves survival over Osi monotherapy. OS difference was about 10 months at 47 vs 37 months, with a predictable toxicity tradeoff.

Updated Overall Survival Analysis From the Phase II PHAROS Study of Encorafenib Plus Binimetinib in Patients With BRAF V600E-Mutant Metastatic Non–Small Cell Lung Cancer

This update demonstrated that encorafenib plus binimetinib was associated with the longest median overall survival (mOS) reported to date among targeted therapies in patients with treatment-naïve BRAF V600E–mutant metastatic NSCLC (mNSCLC). Median OS was 47.6 months in treatment-naïve patients. By the way check the authors there 😊.

Simultaneous Durvalumab and Platinum-Based Chemoradiotherapy in Unresectable Stage III Non–Small Cell Lung Cancer: The Phase III PACIFIC-2 Study

PACIFIC-2 was a phase III trial testing durva given concurrently with cCRT (and continued as consolidation) versus placebo + cCRT in unresectable stage III NSCLC, and it did not meet its primary endpoint. The overall response rate (ORR) was essentially identical (60.7% vs 60.6%), and pneumonitis rates were similar (any grade 28.8% vs 28.7%; grade ≥3: 4.6% vs 5.6%), but adverse events (AEs) leading to discontinuation and fatal AEs were higher with durva (25.6% vs 12.0%; 13.7% vs 10.2%), especially early on. Starting IO up front with cCRT didn’t improve outcomes and added early toxicity—consolidation durva after cCRT is still the way to go.

Sevabertinib in Advanced HER2-Mutant Non–Small-Cell Lung Cancer

Sevabertinib shows strong efficacy in HER2-mutant NSCLC, with an overall response rate (ORR) of 64% and median progression-free survival (PFS) of 8.3 months in previously treated, HER2-TKI–naive patients, and an overall response rate (ORR) of 71% with a duration of response (DOR) of 11.0 months in first-line therapy. Activity is highest in TKD mutations, especially Y772_A775dupYVMA, and intracranial responses are seen. Safety is manageable: diarrhea is common but mostly low grade, with grade ≥3 in 5–23% and rare discontinuations. Notably, interstitial lung disease (ILD) was not observed. These data position sevabertinib as a viable oral TKI alongside ADCs for HER2-mutant NSCLC, particularly for TKD/YVMA disease.