This problem is not new and without ccache VB build is fine.

Error (full log in the attachment):
…
kBuild: Linking VBoxPython
kBuild: Installing VBoxPython => /usr/ports/emulators/virtualbox-ose/work/VirtualBox-5.1.6/out/freebsd.amd64/release/bin/VBoxPython.so
kBuild: Compiling VBoxRemPrimary - /usr/ports/emulators/virtualbox-ose/work/VirtualBox-5.1.6/src/recompiler/VBoxRecompiler.c
cc1: error: to generate dependencies you must specify either -M or -MM
kmk: *** [/usr/ports/emulators/virtualbox-ose/work/VirtualBox-5.1.6/out/freebsd.amd64/release/obj/VBoxRemPrimary/VBoxRecompiler.o] Error 1
The failing command:
@gcc48 -c -O2 -g -pipe -O2 -mtune=generic -fno-omit-frame-pointer -fno-strict-aliasing -fvisibility=hidden -DVBOX_HAVE_VISIBILITY_HIDDEN -DRT_USE_VISIBILITY_DEFAULT -fPIC -Wno-sign-compare -Werror-implicit-function-declaration -m64 -I/usr/ports/emulators/virtualbox-ose/work/VirtualBox-5.1.6/src/recompiler/Sun/crt -I/usr/ports/emulators/virtualbox-ose/work/VirtualBox-5.1.6/src/recompiler/Sun -I/usr/ports/emulators/virtualbox-ose/work/VirtualBox-5.1.6/src/recompiler/target-i386 -I/usr/ports/emulators/virtualbox-ose/work/VirtualBox-5.1.6/src/recompiler/tcg -I/usr/ports/emulators/virtualbox-ose/work/VirtualBox-5.1.6/src/recompiler/fpu -I/usr/ports/emulators/virtualbox-ose/work/VirtualBox-5.1.6/out/freebsd.amd64/release/obj/VBoxRemPrimary -I/usr/ports/emulators/virtualbox-ose/work/VirtualBox-5.1.6/src/VBox/VMM/include -I/usr/ports/emulators/virtualbox-ose/work/VirtualBox-5.1.6/src/recompiler/tcg/i386 -I/usr/ports/emulators/virtualbox-ose/work/VirtualBox-5.1.6/src/recompiler -I/usr/local/include -I/usr/ports/emulators/virtualbox-ose/work/VirtualBox-5.1.6/out/freebsd.amd64/release/obj/VBoxRemPrimary/dtrace -I/usr/ports/emulators/virtualbox-ose/work/VirtualBox-5.1.6/include -I/usr/ports/emulators/virtualbox-ose/work/VirtualBox-5.1.6/out/freebsd.amd64/release -DVBOX -DVBOX_OSE -DVBOX_WITH_64_BITS_GUESTS -DVBOX_WITH_REM -DVBOX_WITH_RAW_MODE -DRT_OS_FREEBSD -D__FREEBSD__ -DRT_ARCH_AMD64 -D__AMD64__ -DVBOX_WITH_DEBUGGER -DVBOX_WITH_HARDENING -DRTPATH_APP_PRIVATE=\"/usr/local/share/virtualbox-ose\" -DRTPATH_APP_PRIVATE_ARCH=\"/usr/local/lib/virtualbox\" -DRTPATH_SHARED_LIBS=\"/usr/local/lib/virtualbox\" -DRTPATH_APP_DOCS=\"/usr/local/share/doc/virtualbox-ose\" -DIN_RING3 -DHC_ARCH_BITS=64 -DGC_ARCH_BITS=64 -DPIC -DIN_REM_R3 -DREM_INCLUDE_CPU_H -DNEED_CPU_H -DVBOX_WITH_NEW_APIC -DVBOX_WITH_RAW_MODE -DVBOX_WITH_RAW_RING1 -DLOG_USE_C99 -D_BSD -D__x86_64__ -Wp,-MD,/usr/ports/emulators/virtualbox-ose/work/VirtualBox-5.1.6/out/freebsd.amd64/release/obj/VBoxRemPrimary/VBoxRecompiler.o.dep -Wp,-MT,/usr/ports/emulators/virtualbox-ose/work/VirtualBox-5.1.6/out/freebsd.amd64/release/obj/VBoxRemPrimary/VBoxRecompiler.o -Wp,-MP -o /usr/ports/emulators/virtualbox-ose/work/VirtualBox-5.1.6/out/freebsd.amd64/release/obj/VBoxRemPrimary/VBoxRecompiler.o /usr/ports/emulators/virtualbox-ose/work/VirtualBox-5.1.6/src/recompiler/VBoxRecompiler.c
*** Error code 2

Stop.
make[1]: stopped in /usr/ports/emulators/virtualbox-ose
*** Error code 1

Stop.
make: stopped in /usr/ports/emulators/virtualbox-ose

root@vladiom:~ # pkg version -v | grep -e virtualbox -e ccache
ccache-3.2.5_2                     =   up-to-date with index
virtualbox-ose-5.1.6               =   up-to-date with index
virtualbox-ose-kmod-5.1.6          =   up-to-date with index

<uname>
FreeBSD 10.3-RELEASE-p7 amd64

<make.conf>
CPUTYPE?=core2
OPTIONS_SET=CUPS
WITHOUT_LPR=YES
DEFAULT_VERSIONS+=apache=2.4
QT4_OPTIONS=CUPS NAS QGTKSTYLE
LOCALIZED_LANG=ru
DEFAULT_VERSIONS+=perl5=5.20
MAKE_JOBS_UNSAFE=yes
DEFAULT_VERSIONS+=mysql=5.7
.if ${.CURDIR:M*/ports/devel/ccache}
NO_CCACHE=yes
.endif
DEFAULT_VERSIONS+=ssl=openssl
CC=clang37
CXX=clang++37
CPP=clang-cpp37