European Cancer Congress Highlights Oncology News Roundup

Top cancer-related news from the past week.

Top cancer-related news from the past week.

Cabozantinib Shows Big PFS Advantage Versus Everolimus

Treatment with the multikinase inhibitor cabozantinib reduced the risk of progression or death by 42% compared with everolimus in patients with previously treated advanced renal cell carcinoma. After a minimum of 11 months of follow-up for the first 375 patients enrolled in the open-label trial, the median progression-free survival with cabozantinib was 7.4 months compared with 3.8 months with everolimus (HR, 0.58; 95% CI, 0.45-0.75; P <.001).

In this same group, the objective response rate was 21% in those treated with cabozantinib versus 5% with everolimus (P <.001). At the interim analysis of the full study population (n = 658), a trend toward improvement in overall survival was observed; however, this did not yet pass a high bar (P ≤.0019) for statistical significance (HR, 0.67; 95% CI, 0.51-0.89; P = .005). The survival follow-up will continue until the data mature. Data from this study will be submitted to the FDA, under a breakthrough therapy designation.

See more at: http://www.onclive.com/conference-coverage/ecc-2015/second-line-cabozantinib-improves-pfs-in-advanced-rcc

Nivolumab Improves Survival in RCC

Nivolumab reduced the risk of death by 27% versus everolimus in patients with advanced renal cell carcinoma. At a minimum follow-up of 14 months, the median overall survival was 25.0 months with nivolumab versus 19.6 months with everolimus (HR, 0.73; 98.5% CI, 0.57-0.93; P = .002), representing a 5.4-month improvement.

Median progression-free survival was 4.6 and 4.4 months in the nivolumab and everolimus arms, respectively (HR, 0.88; 95% CI, 0.75-1.03; P = .11). This may have been caused by pseudoprogression. To compensate for this, an ad hoc sensitivity analysis of PFS was conducted in patients who had not progressed at 6 months. The median PFS in this cohort was 15.6 months with nivolumab versus 11.7 months with everolimus (HR, 0.64; 95% CI, 0.47-0.88).

The rate of grade 3/4 toxicities was lower with nivolumab at 19% versus 37% with everolimus. The FDA recently granted nivolumab a breakthrough therapy designation for the treatment of patients with advanced RCC, which will expedite the development and regulatory review.

See more at: http://www.onclive.com/conference-coverage/ecc-2015/nivolumab-extends-survival-in-advanced-renal-cell-carcinoma

Atezolizumab Effective Across Two Pivotal NSCLC Studies

Inhibition of PD-L1 with atezolizumab demonstrated significant clinical efficacy as monotherapy in patients with advanced non-small cell lung cancer. At a minimum follow-up of 6 months in the phase II BIRCH trial, more than 61% of responses were ongoing.

Tumor shrinkage was observed in up to 27% of patients whose disease progressed following prior treatment and who expressed PD-L1 at the highest levels (P = .0001). In the phase II POPLAR study, patients with the highest level of PD-L1 expression experienced a median overall survival with atezolizumab of 15.5 months compared with 11.1 months for docetaxel (HR, 0.49; 95% CI, 0.22-1.07; P = .068). Atezolizumab was granted a breakthrough therapy designation for patients with PD-L1-positive NSCLC in February 2015.

Building on this designation, Genentech is currently in discussions with the FDA on the submission of data from POPLAR and BIRCH.

See more at: http://www.onclive.com/conference-coverage/ecc-2015/two-pivotal-studies-show-efficacy-of-atezolizumab-in-pd-l1-positive-nsclc

Atezolizumab Effective in Urothelial Carcinoma

Second-line atezolizumab demonstrated significant clinical benefit in patients with metastatic urothelial carcinoma who had a poor prognosis after progressing following platinum-based chemotherapy. In the first-line setting for those who were PD-L1 positive, the ORR was 26%.

In the second- and third-line setting, the ORRs with atezolizumab were 39% and 20%, respectively. The median duration of response had not been reached at the time of cutoff but demonstrated a range of 0+ to 43 months. Median PFS at a follow-up of 24 weeks was 2.1 months across all groups. OS data were not yet mature. Atezolizumab demonstrated activity previously in metastatic urothelial carcinoma, leading to a breakthrough designation from the FDA in 2014.

Results from the ECC study will be submitted under this designation to the FDA, since there is currently a high, unmet need for viable treatments in metastatic urothelial carcinoma.

See more at: http://www.onclive.com/conference-coverage/ecc-2015/atezolizumab-provides-viable-treatment-option-in-metastatic-urothelial-carcinoma

Everolimus Likely New Standard of Care for Lung, GI NETs

Treatment with everolimus was associated with a 52% reduction in the risk of progression or death compared with placebo in patients with advanced lung and GI neuroendocrine tumors. In the phase III study, the primary endpoint of progression-free survival as assessed by central radiology review was a median 11.0 months with everolimus compared with 3.9 months with placebo (HR, 0.48; 95% CI, 0.35-0.67; P < .001).

This “robust benefit” was confirmed in the investigator-assessed PFS, which was 14.0 months compared with 5.5 months with placebo (HR, 0.39; 95% CI, 0.28—0.54; P < .001). These data will be prepared and submitted to the FDA.

See more at: http://www.onclive.com/conference-coverage/ecc-2015/everolimus-may-be-new-standard-of-care-in-advanced-lung-gi-nets

Radionuclide Therapy Highly Effective in Midgut NETs

Treatment with the novel peptide receptor radionuclide therapy Lutathera significantly increased progression-free survival over octreotide LAR in patients with advanced midgut neuroendocrine tumors. Lutathera is a novel agent that attaches to somatostatin receptors to release a cytotoxic radiotherapy directly to the tumor.

After a median 30 months of follow-up of 229 patients in the intent-to-treat population of the NETTER-1 trial, the median PFS with Lutathera was not reached compared with 8.4 months with octreotide LAR (HR, 0.209; 95% CI, 0.129-0.338), providing a risk reduction of 79.1% (P <.0001). In the Lutathera cohort, ORR was 19% versus 3% with octreotide LAR.

Overall, the agent was found to be safe, with tolerable toxicity. OS data from the study are not yet mature. The results will likely be submitted to the FDA for regulatory approval.

See more at: http://www.onclive.com/conference-coverage/ecc-2015/targeted-radionuclide-improves-pfs-over-octreotide-lar-in-midgut-nets

Trabectedin OS Data Confounded

The final analysis of phase III data for trabectedin were consistent with interim results by showing a lack of improvement for the primary endpoint of overall survival in patients with advanced soft tissue sarcoma. After a 21-month follow-up, the median OS with trabectedin was 13.7 months compared with 13.1 months with dacarbazine (HR, 0.93; 95% CI, 0.75-1.15; P = .492).

The median progression-free survival with trabectedin was 4.2 versus 1.5 months with dacarbazine (HR, 0.55; 95% CI, 0.44-0.70; P <.001). The lack of OS was explained by a 47% longer median time to initiation of subsequent therapies in patients treated with trabectedin. The next therapy was initiated after a median of 6.8 months in those receiving trabectedin versus 3.5 months for those in the dacarbazine arm (HR, 0.53; P <.0001).

Giant of Cancer Care George Demetri, MD, noted that OS is a controversial endpoint in sarcoma, which is often confounded by subsequent therapies. In this setting, the benefits seen in PFS are clinically meaningful and important for patients. The FDA is currently reviewing an application for trabectedin. The drug is already approved across many locations worldwide.

See more at: http://www.onclive.com/conference-coverage/ecc-2015/trabectedin-os-data-unclear-in-phase-iii-sarcoma-study

Dabrafenib/Trametinib OS Extended With Longer Follow-up

The combination of dabrafenib plus trametinib improved overall survival by 7.6 months compared with single-agent vemurafenib in patients with unresectable or metastatic BRAFV600E/K-mutant melanoma, according to a 2-year analysis of the phase III COMBI-v study. At the longer analysis, the median OS with dabrafenib/trametinib was 25.6 months compared with 18 months with vemurafenib (HR, 0.66; 95% CI, 0.53-0.81; P <.001). The estimated 2-year OS rate was 51% with the combination compared with 38% with vemurafenib monotherapy.

The combination currently has an accelerated approval. An application for full approval was submitted to the FDA in July 2015, based on findings from the COMBI-v and COMBI-d studies. In the phase III COMBI-d trial, the combination demonstrated a median OS of 25.1 months compared with 18.7 months with dabrafenib alone (HR, 0.71; 95% CI, 0.55-0.92; P = .011). A decision is expected by November 11, 2015.

See more at: http://www.onclive.com/conference-coverage/ecc-2015/dabrafenib-trametinib-combo-improves-os-versus-vemurafenib-in-advanced-melanoma

Nivolumab OS Benefit Extended With Longer Assessment

Treatment with the PD-1 inhibitor nivolumab reduced the risk of death by 28% compared with docetaxel for patients with previously treated nonsquamous non—small cell lung cancer, according to updated findings from the phase III CheckMate-057 study.

At a minimum follow-up of 17.2 months, the overall survival rate with nivolumab was 39% compared with 23% for docetaxel. The median OS with nivolumab was 12.2 versus 9.4 months with docetaxel (HR, 0.72; 95% CI, 0.60-0.88; P <.001). The 1-year progression-free survival rates were 19% and 8% and the objective response rates were 19% and 12%, with nivolumab and docetaxel, respectively.

Adverse events were significantly less frequent with nivolumab compared with docetaxel. The rates of all-grade AEs were 69% and 88%, with nivolumab and docetaxel. Grade 3/4 AEs occurred in 10% of patients treated with nivolumab compared with 54% for docetaxel. On September 2, 2015, the FDA granted nivolumab both a breakthrough therapy designation and a priority review for patients with previously treated nonsquamous NSCLC.

Under this expedited review process, the FDA’s decision deadline is January 2, 2016.

See more at: http://www.onclive.com/conference-coverage/ecc-2015/longer-follow-up-confirms-nivolumab-os-benefit-in-nonsquamous-nsclc

First Effective Targeted Therapy for SCLC

The antibody-drug conjugate rovalpituzumab tesirine showed activity across a range of patients with relapsed and refractory small-cell lung cancer, representing the first demonstration of efficacy for a targeted therapy in this setting. In the phase I study, patients with SCLC who were sensitive to first-line combination chemotherapy and were positive for DLL3 gene expression experienced an objective response rate of 64% with Rova-T.

In the third-line setting, where a standard treatment is currently not available, the ORR in DLL3-expressing patients (n = 15) was 45%. Across all patients in the third-line setting, regardless of DLL3 expression (n = 35), the ORR was 20%. In the second-line setting, the ORR was 44%. Patients who were refractory or resistant to first-line therapy had an ORR of 23%.

See more at: http://www.onclive.com/conference-coverage/ecc-2015/novel-antibody-drug-conjugate-shows-promise-in-sclc

FDA Grants Nivolumab/Ipilimumab Combo Priority Review

The FDA granted a priority review designation to a supplemental biologics license application for nivolumab plus ipilimumab in previously untreated patients with advanced melanoma. The new application for nivolumab plus ipilimumab was based on findings from the phase III CheckMate-067 trial.

At greater than 9 months of follow up, the median progression-free survival was 11.5 months for the combination, 6.9 months for nivolumab monotherapy, and 2.9 months for single-agent ipilimumab. The combination reduced the risk of progression by 58% compared with ipilimumab (HR, 0.42; P <.0001).

A previous application for the nivolumab/ipilimumab combination was submitted in early 2015, based on data from the phase II CheckMate-069 trial. For the new application, the FDA will make a decision by January 23, 2016.

See more at: http://www.onclive.com/web-exclusives/fda-grants-nivolumabipilimumab-combination-priority-review-for-advanced-melanoma

TAS-102 Approved for mCRC

The FDA recently approved the oral nucleoside TAS-102 for the treatment of patients with metastatic colorectal cancer who have previously received fluoropyrimidine-, oxaliplatin- , and irinotecan-based chemotherapy, an anti-VEGF biologic product, and an anti-EGFR monoclonal antibody, if RAS wild-type. The approval, which is based on the phase III RECOURSE trial, comes 2 months ahead of the FDA's scheduled action date.

In the pivotal study, the median overall survival for patients with mCRC who received TAS-102 was 7.1 months compared with 5.3 months with placebo (HR, 0.68; P <.0001). The median progression-free survival in the TAS-102 arm was 2 months versus 1.7 months with placebo (HR, 0.48; P <.0001).

The 1-year OS rate with TAS-102 was 27% compared with 18% with placebo. The ORR was 1.6% with TAS-102, which consisted of a complete response in 1 patient and partial responses. The ORR with placebo was 0.4% (P = .29).

See more at: http://www.onclive.com/web-exclusives/fda-approves-tas-102-for-advanced-colorectal-cancer