ASCO Highlights: Lambrolizumab in advanced melanoma; pomalidomide with dexamethasone and PLD in multiple myeloma

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Genitourinary (Prostate) Cancer

Effect of corticosteroid (CS) use at baseline (CUB) on overall survival (OS) in patients (pts) receiving abiraterone acetate (AA): Results from a randomized study (COU-AA-301) in metastatic castration-resistant prostate cancer (mCRPC) post-docetaxel (D)

Robert B. Montgomery, MD

In this study, CUB was not a strong independent prognostic factor in mCRPC post-docetaxel pts treated with AA + prednisone or prednisone alone. CUB was associated with worse baseline disease characteristics and inferior OS in this study, in which all pts subsequently received corticosteroid.

ERG rearrangements and association with clinical outcome in patients (pts) receiving abiraterone acetate (AA): Results from the COU-AA-302 study in chemotherapy (chemo)-naïve metastatic castration-resistant prostate cancer (mCRPC)

Gerhardt Attard, MD, PhD

This represents the largest study to date to molecularly characterize CRPC pts participating in a therapeutic phase 3 trial. These data suggest that chemo-naïve mCRPC pts with a 2+ Edel rearrangement may derive a slightly greater benefit from abiraterone acetate and prednisone than other pts.

Breast Cancer

Clinical and translational results of CALGB 40601: A neoadjuvant phase III trial of weekly paclitaxel and trastuzumab with or without lapatinib for HER2-positive breast cancer

Lisa A. Carey, MD

Pathological complete response (pCR) rate was higher with combined THL compared with standard TH but did not reach statistical significance. These results are qualitatively similar to other neoadjuvant studies in HER2+ BrCa, and contribute to estimates of pCR rates after these agents. Tissue-based studies may illuminate which patients benefit from HER2-targeting using these agents.

Follow-up results of NOAH, a randomized phase III trial evaluating neoadjuvant chemotherapy with trastuzumab (CT+H) followed by adjuvant H versus CT alone, in patients with HER2-positive locally advanced breast cancer

Luca Gianni, MD

Present analysis confirms the significant event-free survival benefit observed in the primary analysis of the NOAH study, and shows a strong trend towards improved OS with the addition of trastuzumab to chemotherapy. pCR rate may be considered as a possible primary endpoint and early indicator of benefit in future neoadjuvant studies of HER2-targeted agents.

Phase III, randomized, double-blind, placebo-controlled multicenter trial of daily everolimus plus weekly trastuzumab and vinorelbine in trastuzumab-resistant, advanced breast cancer (BOLERO-3)

Ruth O'Regan, MD

Head and Neck Cancer

As of February 4, 2013, a total of 396 PFS events were reported.Efficacy of cabozantinib (Cabo) in medullary thyroid cancer (MTC) patients with RAS or RET mutations: Results from a phase III study

Steven I. Sherman, MD

While hazard ratios indicate PFS improvement for all RET subgroups on cabo, the extent of benefit may depend in part on RET genotype. Cabo treatment benefit is also seen in pts harboring a RAS mutation

A phase II-III study comparing concomitant chemoradiotherapy (CRT) versus cetuximab/RT (CET/RT) with or without induction docetaxel/cisplatin/5-fluorouracil (TPF) in locally advanced head and neck squamous cell carcinoma (LASCCHN): Efficacy results (NCT01086826)

Maria G. Ghi, MD

No significant differences were observed in response rate, progression free survival and OS between CRT and CET/RT. Pts are still being followed-up to assess OS of induction vs. no induction arms.

Melanoma/Skin Cancers

Clinical efficacy and safety of lambrolizumab (MK-3475, Anti-PD-1 monoclonal antibody) in patients with advanced melanoma

Antoni Ribas, MD

Preliminary data suggest that lambrolizumab has significant antitumor activity and is well tolerated with manageable side effects in both IPI-naive and IPI-pretreated melanoma pts. These data have led to an ongoing, international, randomized study of lambrolizumab versus chemotherapy in IPI-pretreated melanoma.

Clinical activity, safety, and biomarkers of MPDL3280A, an engineered PD-L1 antibody in patients with locally advanced or metastatic melanoma (mM)

Omid Hamid, MD

MPDL3280A was well tolerated as monotherapy, and durable ORs were observed. Therefore, further assessment of MPDL3280A as monotherapy and combination therapy is warranted.

Leukemia, Myelodysplasia, and Transplantation

MEDI-551, an anti-CD19 antibody active in chronic lymphocytic leukemia (CLL) patients previously treated with rituximab

Single-agent activity with a manageable toxicity profile was seen in CLL pts treated in this phase 1/2 study of MEDI-551. An ongoing phase 2 study of MEDI-551 in combination with bendamustine in relapsed CLL patients (NCT01466153) is evaluating clinical response to MEDI-551 and chemotherapy.

A phase II study of mocetinostat, an oral isotype-selective histone deacetylase (HDAC) inhibitor, in combination with 5-azacitidine in patients with myelodysplastic syndrome (MDS)

The combination of mocetinostat and 5-azacitidine in patients with MDS demonstrated an acceptable safety profile and encouraging evidence of clinical benefit. Further clinical studies are warranted.

Lymphoma and Plasma Cell Disorders

A phase II study of gemcitabine, ifosfamide, and oxaliplatin (GIFOX) as upfront treatment for high-risk, non-anaplastic large cell, peripheral T-cell lymphomas

Response and survival rates of GIFOX in high-risk PTCL compared more than favorably to CHOP-based regimens. Effective cytoreduction and prompt access to autologous transplantation (ASCT) were ensured, together with safe delivery of a full induction program to transplant-ineligible pts.

A phase I/II study (NCT01541332) of pomalidomide (POM), dexamethasone (DEX), and pegylated liposomal doxorubicin (PLD) for patients with relapsed/refractory (R/R) multiple myeloma (MM)

The combination of pomalidomide with dexamethasone and PLD on a 28-day cycle shows efficacy for R/R MM pts. However, because of excessive ≥ G3 neutropenia, POM is being reduced to 3 mg for newly enrolled patients.

Results of a phase I/II study (NCT01365559) of carfilzomib (CFZ) replacing bortezomib (BTZ) in BTZ-containing regimens for BTZ-treated patients (pts) with relapsed and refractory multiple myeloma (MM).

Gastrointestinal (Noncolorectal) Cancer

FOLFIRI plus sunitinib versus FOLFIRI alone in advanced chemorefractory esophagogastric cancer patients: A randomized placebo-controlled multicentric AIO phase II trial

In our phase II trial, Sunitinib added to FOLFIRI increased hematotoxicity and did not improve response rates or PFS in chemotherapy-resistant GC patients. Since the regimen was safe and patients had a trend to better OS, biomarker analyses will be performed to identify subgroups that benefit from add-on Sunitinib.

These results suggest that replacement of BTZ with CFZ in a BTZ-containing combination regimen to which a MM patient is failing often leads to responses and is well-tolerated.

Multicenter, phase II study of trastuzumab and paclitaxel to treat HER2-positive, metastatic gastric cancer patients naive to trastuzumab (JFMC45-1102)

Combination chemotherapy of paclitaxel plus trastuzumab showed promising activity and was tolerated well by patients naïve to trastuzumab who were positive for HER2 and treated previously for metastatic gastric cancer (mGC)

Overall survival (OS) analysis from PRIME: Randomized phase III study of panitumumab (pmab) with FOLFOX4 for first-line metastatic colorectal cancer (mCRC)

In this updated analysis, an improvement in OS was observed in pts with wild-type (WT) KRAS exon 2 mCRC treated with pmab + FOLFOX4 vs FOLFOX4 alone (p = 0.03). Median OS was reduced in pts with mutant (MT) KRAS mCRC (p = 0.16) and is consistent with previous analyses. Updated efficacy and safety results will be presented. KRAS testing is critical to select appropriate pts with mCRC for treatment with pmab.

Analysis of overall survival and safety during the course of the phase III VELOUR trial comparing FOLFIRI and ziv-aflibercept or placebo in mCRC patients who progressed on prior oxaliplatin treatment

Treatment with ziv-aflibercept/FOLFIRI showed continuous, consistent improvement in OS over time. While combined grade 3/4 AEs were higher with ziv-aflibercept, AEs occurred early in treatment in a small proportion of total cycles; the majority were single-episode in nature.

Results of a phase III, randomized, double-blind, placebo-controlled trial of pegfilgrastim (PEG) in patients (pts) receiving first-line FOLFOX or FOLFIRI and bevacizumab (B) for colorectal cancer (CRC)

PEG significantly reduced the incidence of grade 3/4 FN in this pt population receiving standard chemotherapybevacizumab for CRC. Follow-up is ongoing.

Comprehensive analysis of KRAS and NRAS mutations as predictive biomarkers for single agent panitumumab (pmab) response in a randomized, phase III metastatic colorectal cancer (mCRC) study (20020408)

This exploratory analysis suggests that mutations in KRAS and NRAS exon 4 occur in a small, but meaningful percentage of patients with mCRC. Extending previous findings from this study in patients with mutant KRAS and/or mutant NRAS exon 2 and/or 3 tumors, patients with mutant KRAS and/or mutant NRAS exon 4 tumors do not appear to benefit from pmab therapy.

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